Tofacitinib citrate

Mechanism Of Action:

Tofacitinib exerts its mechanism of action by inhibiting intracellular cytoplasmic non-receptor tyrosine kinase JAK enzymes, which are involved in adaptive and innate immune reactions in the process of immune-mediated inflammatory diseases.  It is a reversible and competitive JAK inhibitor that binds to the ATP binding site of the kinase domain of JAK. It is similar in structure to ATP and binds to the ATP-binding site of JAK, thus competing with ATP for binding to the active site of the kinase domain. As a result, the drug inhibits the phosphorylation and activation of JAK, thereby preventing the phosphorylation and activation of STATs, and thus the activation of gene transcription; this leads to decreased cytokine production and modulation of the immune response. Tofacitinib is a pan-JAK inhibitor but targets JAK1 and JAK3 with a higher specificity over JAK2 and TYK2.

Indication:

Tofacitinib is used to treat adults who have tried TNF blockers with:

• Moderately to severely active rheumatoid arthritis when one or more medicines called tumor necrosis factor (TNF) blockers have been tried, and did not work well or cannot be tolerated.
• Active psoriatic arthritis when one or more TNF blocker medicines have been tried, and did not work well or cannot be tolerated.
• Moderately to severely active ulcerative colitis when one or more TNF blocker medicines have been tried, and did not work well or cannot be tolerated.
• Active ankylosing spondylitis when one or more TNF blocker medicines have been tried, and did not work well or cannot be tolerated.

Tofacitinib Oral Solution is used to treat patients 2 years of age and older with:

• Active polyarticular course juvenile arthritis when one or more TNF blocker medicines have been tried, and did not work well or cannot be tolerated.