Difference Between Baricitinib Tofacitinib and Upadacitinib

The key difference between baricitinib tofacitinib and upadacitinib is that baricitinib is an inhibitor of Jak1 and Jak2 while tofacitinib is an inhibitor of Jak1 and Jak3 and upadacitinib is a selective inhibitor of Jak1.

Janus kinase or JAK is a family of cytoplasmic non-receptor tyrosine kinase proteins. They are associated with cytokine receptors and activate members of signal transducer and activator of transcription (STAT) family of transcription factors. There are Janus kinase inhibitors. Tofacitinib, baricitinib, and upadacitinib are the three types of novel selective oral Janus activated kinase inhibitors in rheumatoid arthritis (RA).

RA is a chronic systemic autoimmune disease characterized by persistent joint damage and extra-articular manifestations affecting many other organ systems. Cytokines are critical drivers of inflammation in RA. JAKs mediate downstream signaling of multiple cytokines and growth factors involved inflammatory and autoimmune disorders. Jak inhibitors are approved for the treatment of RA. Jak inhibitors selectively inhibit jak isoforms which are jak1, jak2, jak3 and tyk2. Tofacitinib inhibits Jak1 and Jak3 while baricitinib inhibits Jak1 and Jak2. Upadacitinib selectively inhibits Jak1.

CONTENTS

1. Overview and Key Difference
2. What is Baricitinib 
3. What is Tofacitinib 
4. What is Upadacitinib
5. Similarities Between Baricitinib Tofacitinib and Upadacitinib
6. Side by Side Comparison – Baricitinib vs Tofacitinib vs Upadacitinib in Tabular Form
7. Summary

What is Baricitinib?

Baricitinib (brand name Olumiant) is a drug for the treatment of rheumatoid arthritis (RA) in adults. It acts as an inhibitor of janus kinase (JAK), blocking the subtypes JAK1 and JAK2. This drug interferes with the inflammatory processes within the immune system that lead to the symptoms of RA.  Baricitinib is an approved drug for moderately to severely active RA in adults over 60 countries. Baricitinib comes as tablets.

Figure 01: Baricitinib

Long term treatment with baricitinib is effective in treating RA. Before starting the treatments for RA using baricitinib, it is very important to confirm whether you have previously been exposed to tuberculosis (TB) or hepatitis. Before starting baricitinib, it is necessary to undergo a course of treatment for latent (asymptomatic) TB. When considering hepatitis, baricitinib may increase the risk of the reactivation of hepatitis.

What is Tofacitinib?

Tofacitinib (brand name Xeljanz) is another Jak inhibitor which is used to treat rheumatoid arthritis (RA), psoriatic arthritis, and ulcerative colitis. It is also used to treat a certain bowel disease (ulcerative colitis). It helps to reduce symptoms of ulcerative colitis such as diarrhea, rectal bleeding, and stomach pain. It is a small molecule that inhibits jak isoforms 1 (jak1) and 3 (jak3).

Figure 02: Tofacitinib

Basically, tofacitinib interferes with the JAK-STAT signaling pathway by blocking the body’s production of enzymes. Tofacitinib is available as tablets. It is taken orally. Similar to baricitinib, tofacitinib is a long-term treatment.

What is Upadacitinib?

Upadacitinib (brand name Rinvoq) is a jak inhibitor similar to baricitinib and tofacitinib. It is a second-generation drug which inhibits Jak1 selectively by blocking the action of enzymes leading to inflammation. Therefore, it is used to treat moderate to severe active rheumatoid arthritis in adults. It can be used in combination with methotrexate as well. When compared with baricitinib and tofacitinib, upadacitinib has subtype selectivity.

Figure 03: Upadacitinib

Upadacitinib can cause several side effects, including upper respiratory tract infections such as common cold and sinus infections, etc., nausea, cough, and fever. Apart from these common side effects, upadacitinib can cause severe side effects, including pneumonia, cellulitis and tuberculosis.

What are the Similarities Between Baricitinib Tofacitinib and Upadacitinib?

• Baricitinib, tofacitinib and upadacitinib are types of Janus kinase (JAK) inhibitor medication or drugs.
• The three are approved drugs.
• Both significantly improve RA control.
• They are taken orally.

What is the Difference Between Baricitinib Tofacitinib and Upadacitinib?

Baricitinib is a Jak inhibitor which inhibits Jak isoforms 1 and 2 while Tofacitinib is first-generation jak inhibitor that inhibits subtypes Jak1 and Jak3. Upadacitinib is a second-generation Janus kinase inhibitor that is selective for Jak1. So, this is the key difference between baricitinib tofacitinib and upadacitinib. Olumiant is the brand name of baricitinib while Xeljanz and Rinvoq are brand names of tofacitinib and upadacitinib, respectively.

The below infographic tabulates side by side more differences between baricitinib tofacitinib and upadacitinib.

Summary – Baricitinib vs Tofacitinib vs Upadacitinib

Baricitinib, tofacitinib and upadacitinib are oral Jak inhibitors. They are approved drugs used to treat adults with moderately to severely active rheumatoid arthritis. Baricitinib inhibits Jak1 and 2 while tofacitinib inhibits Jak1 and 3. Upadacitinib selectively inhibits Jak1. Their brand names are Olumiant, Xeljanz and Rinvoq, respectively. Thus, this summarizes the difference between baricitinib tofacitinib and upadacitinib.

Reference:

1. “Baricitinib.” Versus Arthritis, Available here.
2. O’Shea, John J, et al. “Janus Kinase Inhibitors in Autoimmune Diseases.” Annals of the Rheumatic Diseases, U.S. National Library of Medicine, Apr. 2013, Available here.

Image Courtesy:

1. “Baricitinib-portrait-ligand-3JW-from-PDB-xtal-4W9X-Mercury-3D-balls” By Ben Mills – Own work (Public Domain) via Commons Wikimedia
2. “Tofacitinib” By Vaccinationist – Own work, based on PubChem (Public Domain) via Commons Wikimedia
3. “Upadacitinib” By jmorris0x0 – Own work (CC BY-SA 4.0) via Commons Wikimedia

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