Filgotinib

Filgotinib is an orally administered Janus kinase inhibitor 1 (JAK1) developed by Galapagos NV, approved in Europe and Japan for the treatment of moderate-to-severe active rheumatoid arthritis (RA) in adult patients. who have had an inadequate response or are intolerant to disease-modifying ant rheumatic drugs (DMARDs). In India, filgotinib is not currently approved for any indication.

BRAND NAME:

Jyseleca – It is available in the form of film coated tablets with strength 100mg & 200mg containing Filgotinib as the main active ingredient.

MECHANISM OF ACTION:

Filgotinib selectively inhibits JAK1, a key enzyme in the JAK-STAT signaling pathway that mediates the activity of several proinflammatory cytokines involved in autoimmune diseases. Its preferential inhibition of JAK1 over other JAK isoforms (JAK2, JAK3, and TYK2) is thought to reduce the risk of side effects associated with pan-JAK inhibitors.

PHARMACOKINETICS:

Absorption:After oral administration, filgotinib is rapidly absorbed, reaching peak plasma concentrations (Tmax) within 2 to 3 hours, with an oral bioavailability of approximately 80% to 90%.

Distribution:Filgotinib exhibits a moderate volume of distribution (~103 liters), indicating good tissue penetration, and binds to plasma proteins at a relatively low rate (~55%).

Metabolism: It is primarily metabolized via hydrolysis by the carboxylesterase 2 (CES2) enzyme, largely in the liver and intestine, producing a major active metabolite, GS-829845. This metabolite has approximately tenfold lower potency at JAK1 compared to filgotinib but circulates at significantly higher systemic concentrations.

Excretion: 87% of drug is excreted through urine and the remaining 15% of drug is excreted through feces.

PHARMACODYNAMICS:

Filgotinib is a selective inhibitor of Janus kinase 1 (JAK1), one of the four members of the Janus kinase family, which also includes JAK2, JAK3, and TYK2.These intracellular tyrosine kinases They play a crucial role in mediating cytokine signaling through the JAK-STAT (signal transducer and activator of transcription) pathway. By preferentially targeting JAK1, filgotinib modulates signaling of pro-inflammatory cytokines such as interleukin-6 (IL-6), interferon-γ (IFN-γ), and type I interferons, all of which are implicated in the pathogenesis of autoimmune diseases like rheumatoid arthritis (RA) and ulcerative colitis (UC).

The pharmacodynamic effect of filgotinib is observed through its dose-dependent inhibition of STAT phosphorylation, particularly STAT1, STAT3, and STAT5, in response to cytokine stimulation. This leads to downstream suppression of inflammatory gene transcription, reduction of immune cell activation, and decreased production of inflammatory mediators.

DOSAGE AND ADMINISTRATION:

Filgotinib is available as oral film coated tablets with strengths 100mg & 200mg. The dose recommended basing on the patient health condition, age.

For Rheumatoid arthritis, the recommended dose in adult patients is 200mg once daily. In adults, due to the increased risk of malignancy, the recommended starting dose is 100 mg once daily. If disease control is inadequate, the dose may be increased to 200 mg once daily. For long-term treatment, the lowest effective dose should be maintained.

DRUG INTERACTIONS:

Before taking filgotinib it is recommended to discuss with the doctor if the patient is undergoing treatment for any other diseases. As some medications when interacts with filgotinib can cause severe adverse effects. Below are few drugs that should be avoid while taking filgotinib.