Upadacitinib is among the novel class of medicines with a unique mechanism of action (MOA). It is available by the brand name, Rinvoq that has been approved in 2019 by the FDA.
Among the biological medications, it is one of the few medicines that are available as oral tablet formulations with once-daily dosing.
Rinvoq is used in the treatment of autoimmune rheumatic diseases such as Rheumatoid arthritis, psoriatic arthritis, and atopic dermatitis (Eczema).
Rinvoq for Rheumatoid arthritis:
Upadacitinib (Rinvoq) is used to treat patients with moderate to severe Rheumatoid arthritis.
Rinvoq should be advised only if the person has previously been on a TNF inhibitor and has failed to achieve a clinically meaningful response to TNF inhibitors.
It inhibits the enzyme Janus Kinase which is involved in the activation of immune cells and immune mediators. In patients with Rheumatoid arthritis, it helps in reducing the inflammation, swelling, and pain in the joints.
Because of its strong immune suppressive potential, Upadacitinib is not recommended for use in patients with other strong anti-inflammatory and immunosuppressive drugs. Hence, it should not be given in combination with azathioprine, cyclosporine, or other biological medications.
Entyvio vs Humira (Vedolizumab Vs Adalimumab)
Rinvoq (Upadacitinib) for Psoriatic Arthritis:
Rinvoq has also been approved for the treatment of moderate to severe psoriatic arthritis who have poorly responded to other conventional and biological therapies.
It may be prescribed to patients with psoriatic arthritis who have failed to respond to one or more TNF Inhibitors.
Like in patients with active Rheumatoid Arthritis, Rinvoq is a strong immune-modulating drug that inhibits the function of Janus Kinases.
Janus Kinases are enzymes involved in gene activation and production of inflammatory cytokines.
Read: Biologics for Psoriasis and Psoriatic arthritis
Because it can markedly suppress the immune system and cause neutropenia, it should be avoided in patients who are on other immuno-suppressing drugs like cyclosporin, azathioprine, biological medications, and other JAK inhibitors.
Rinvoq (Upadacitinib) for Atopic Dermatitis:
Atopic dermatitis is a chronic skin condition that can make a person’s life miserable. It is associated with anxiety and loss of self-esteem.
Recently, there has been major breakthrough in the treatment of atopic dermatitis including the use of biological medications such as Dupilumab (Dupixent).
Rinvoq has got FDA approval for patients with moderate to severe atopic dermatitis including children who are 12 years of age or older.
It is only indicated for refractory cases of atopic dermatitis who have not adequately responded to other therapies including biological medications.
Rinvoq may be associated with serious side effects especially opportunistic infections such as tuberculosis and fungal infections.
It is not recommended for use with other concomitant immune-suppressive medications.
Dupilumab MOA (Mechanism of action of Dupixent)
Upadacitinib Mechanism of action (MOA):
Rinvoq is a Janus kinase inhibitor. Janus kinases are a group of enzymes working inside the cells which receive signals from cytokines and affect the processes of formation of new blood cells and functions of cells involved in immunity.
So Upadacitinib (Rinvoq) stops the functioning of Janus kinase and as they can’t receive and respond to signals from the complex network of cytokines, the autoimmune damage is eventually reduced.
It stops the working by preventing the activation and phosphorylation of STATs. As the JAK-STAT pathway is involved in the hematopoiesis and immune functions, inflammation is reduced due to inhibition of these pathways and in this way, Rinvoq proves to be a very helpful cure in treating a devastating disease like Rheumatoid arthritis.
Upadacitnib inhibits STAT 3 phosphorylation by inhibiting Interleukin 6 (JAK1/JAK2). It also inhibits STAT 5 phosphorylation by inhibiting Interleukin 7 (JAK1/JAK3).
Dupixent Side Effects: Dupilumab: Red Eyes, Pain, & Insomnia
Upadacitinib Mechanism of Action Summarized:
Upadacitinib is a strong immune-suppressive drug. It acts by inhibiting JAK enzymes that are involved in the inflammatory cascade.
JAKs (Janus kinases) activate STAT (Signal transducers and activators of transcription) by phosphorylation. When STATs are activated, they activate the inflammatory cytokines.
Upadacitinib inhibits JAKs resulting in the inactivation of STATs and hence reducing inflammatory cytokines.
Thus, Upadacitinib (Rinvoq) modulates intracellular signaling by inhibiting the transcription of genes that are involved in proinflammatory cytokines.