Filgotinib
Filgotinib Uses, Dosage, Side Effects, Food Interaction and all others data.
Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic, and inflammatory disease that causes synovial joint symptoms and can limit range of motion in severe cases. The disease is associated with extra-articular manifestations, progressive disability, and comorbidities including cardiovascular disease and mental disorders. 50-70% of patients with RA are unable to achieve sustained clinical remission despite the availability of several treatments including disease-modifying anti-rheumatic drugs (DMARDS) like methotrexate, interleukin-6 (IL-6) blockers, and tumor necrosis factor (TNF) inhibitors. New therapeutic developments target other inflammatory pathways implicated in RA including the Janus kinase (JAK) signaling pathway as seen with filgotinib.
There are four JAK subtypes which include JAK1, JAK2, JAK3, and tyrosine kinase 2. Non-selective JAK inhibitors like tofacitinib target JAK1 and JAK3 subtypes with minimal activity at JAK2. In contrast, the newly approved filgotinib is a highly selective JAK1 inhibitor. JAK2 and JAK3 play important roles in both immune and hematologic functions; therefore, selectivity for JAK1 aims to improve the safety profile of filgotinib while maintaining clinical efficacy. Filgotinib is currently reserved for patients who cannot tolerate DMARDs, or who have been unable to achieve remission in response to one or more DMARDs.
In addition to targeted Janus kinase (JAK) 1 inhibition, filgotinib targets pro-inflammatory cytokine signalling by inhibiting IL-6 induced STAT1 phosphorylation. Serum C-reactive protein levels are also reduced in response to filgotinib administration.
| Trade Name | Filgotinib |
| Generic | Filgotinib |
| Filgotinib Other Names | Filgotinib |
| Type | |
| Formula | C21H23N5O3S |
| Weight | Average: 425.51 Monoisotopic: 425.152160795 |
| Protein binding | Approximately 55-59% of filgotinib is protein-bound, while 39-44% of the active metabolite GS-829845 is protein-bound. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Filgotinib is a Janus kinase (JAK) 1 selective inhibitor used to treat cases of rheumatoid arthritis that are unresponsive to conventional treatments.
Filgotinib is indicated for the treatment of active moderate to severe rheumatoid arthritis alone or in combination with methotrexate. Filgotinib is currently reserved for patients who are unable to tolerate or who have not responded adequately to one or more disease-modifying anti-rheumatic drugs (DMARDS).
Filgotinib is also used to associated treatment for these conditions: Active, Moderate to Severe Rheumatoid Arthritis
How Filgotinib works
There are four Janus kinase (JAK) enzymes including JAK1, JAK2, JAK3, and tyrosine kinase 2. JAK1 mediates inflammatory cytokine signaling, while JAK2 and JAK3 are important components of hematologic and immune functions. Filgotinib selectively inhibits JAK1 and is for example nearly 30-fold more selective for JAK1 compared to JAK2.
The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is implicated in several inflammatory pathologies and has been found to be continuously active in patients who have RA. Sustained activation of this pathway contributes to aberrant processes which lead to disease progression including elevated levels of matrix metalloproteinases (MMPs) and reduced cell apoptosis in RA affected synovial tissues. Filgotinib acts on the JAK-STAT pathway by selectively inhibiting JAK1 phosphorylation and preventing STAT activation, which ultimately results in reduced proinflammatory cytokine signaling.
Toxicity
Toxicity information regarding filgotinib is not readily available; however, it has been administered in clinical trials at doses of up to 450 mg daily. Associated adverse effects were similar to those observed at lower doses. In the event of overdose, the patient should be closely monitored and supportive measures should be initiated as required.
Food Interaction
No interactions found.Elimination Route
Filgotinib is rapidly absorbed after oral administration. Median peak plasma concentrations occurred 2-3 hours post-dose for filgotinib and 5 hours post-dose for GS-829845. Steady-state concentrations can be observed in 2-3 days for filgotinib and in 4 days for GS-829845. Food does not appear to have a significant effect on the absorption of filgotinib; therefore, the medication can be administered without regard to food.
After repeated oral dosing of filgotinib 200 mg, the reported Cmax and AUCτ values of filgotinib were 2.15 ug/mL and 6.77 ugxh/mL, respectively. For GS-829845 (the major metabolite) the reported Cmax was 4.43 ug/mL and the reported AUCτ was 83.2 ugxh/mL.
Half Life
The half-life of filgotinib is estimated to be 7 hours, while the half-life of its active metabolite GS-829845 is estimated to be 19 hours.
Elimination Route
Of the total administered dose of filgotinib, approximately 87% undergoes renal elimination while 15% undergoes faecal elimination.
Innovators Monograph
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