Baricitinib (Mechanism of Action)

In this article, we will discuss about Baricitinib (Mechanism of Action). So, let’s get started.

Mechanism of action

Baricitinib is a selective and reversible inhibitor of Janus kinase (JAK)1 and JAK2. In isolated enzyme assays, baricitinib inhibited the activities of JAK1, JAK2, Tyrosine kinase 2 and JAK3 with IC50
values of 5.9,5.7,53 and > 400 nM, respectively.

Janus kinases (JAKs) are enzymes that transduce intraacellular signals from cell surface receptors for a number of cytokines and growth factors involved in haematopoiesis, inflammation and immune function. Within the intracellular signalling pathway, JAKs phosphorylate and activate signal transducers and activators of transcription (STATs), which activate gene expression within the cell.
Baricitinib modulates these signalling pathways by partially inhibiting JAK1 and JAK2 enzymatic activity, thereby reducing the phosphorylation and activation of STATs.

Pharmacodynamic Effects

Inhibition of IL-6 induced STAT3 phosphorylation

Administration of baricitinib resulted in a dose dependent inhibition of IL-6 induced STAT3 phosphorylation in whole blood from healthy subjects with maximal inhibition observed 2 hours after dosing which returned to near baseline by 24 hours.


Mean serum IgG, IgM and IgA values decreased by 12 weeks after starting treatment with Baricitinib (Olumiant®), and remained stable at a lower value than baseline through at least 104 weeks. For most patients, changes in immunoglobulins occurred within the normal reference range.


Mean absolute lymphocyte count increased by 1 week after starting treatment with Baricitinib (Olumiant®), returned to baseline by week 24, and then remained stable through at least 104 weeks. For most patients, changes in lymphocyte count occurred within the normal reference range.

C-reactive protein

In patients with rheumatoid arthritis, decreases in serum C-reactive protein (CRP) were observed as early as 1 week after starting treatment with Baricitinib (Olumiant®) and were maintained throughout dosing.


In rheumatoid arthritis, baricitinib induced a mean increase in serum creatinine levels of 3.8 µmol/L after two weeks of treatment, as compared to placebo, which remained stable thereafter during up to 104 weeks of treatment. This may be due to inhibition of creatinine secretion by baricitinib in the renal tubules. Consequently, estimates of the glomerular filtration rate based on serum creatinine may be slightly reduced, without actual loss of renal function or the occurrence of renal adverse events. Similar observations have been made in atopic dermatitis. In atopic dermatitis, baricitinib was
associated with a decrease in eystatin C (also used to estimate glomerular filtration rate) of 0.1 mg/L at week 4. with no further decrease noted up to week 16

In vitro skin models

In an in-vitro human skin model treated with pro-inflammatory cytokines (i.e. IL-4, IL-13. IL-31), baricitinib reduced epidermal keratinocyte pSTAT3 expression, and increased the expression of filaggrin, a protein that plays a role in skin barrier function and in the pathogenesis of atopic dermatitis.

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