Baricitinib, sold under the brand name Olumiant among others, is a drug for the treatment of rheumatoid arthritis in adults whose disease was not well controlled using RA medications called tumor necrosis factor antagonists. It acts as an inhibitor of janus kinase, blocking the subtypes JAK1 and JAK2. The drug is approved for use in the European Union and the United States.
Approvals and indications
In February 2017, Baricitinib was approved for use in the EU as a second-line therapy for moderate to severe active rheumatoid arthritis in adults, either alone or in combination with methotrexate. In April 2017, Baricitinib received a complete response letter from the U.S. Food and Drug Administration, 2017. The letter indicated that the FDA was unable to approve the application in its existing form. Specifically, the FDA indicated that additional clinical data were needed to determine the most appropriate doses and that additional data was necessary to further characterize safety concerns across treatment arms. On 23 April 2018, an FDA Advisory Committee recommended approval of baricitinib 2 mg for the treatment of rheumatoid arthritis but did not recommend the 4 mg dose, citing serious adverse events. On 31 May 2018, FDA approved Barictinib for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies. In the US, baricitinib is indicated for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies.
Contraindications
During pregnancy, the use of baricitinib is contraindicated.
Being metabolized only to a small extent, the substance has a low potential for interactions. In studies, inhibitors of the liver enzymesCYP3A4, CYP2C19, and CYP2C9, as well as the CYP3A4 inducerrifampicin, had no relevant influence on baricitinib concentrations in the bloodstream. While baricitinib blocks a number of transporter proteins in vitro, clinically relevant interactions via this mechanism are considered very unlikely, except perhaps for the cation transporter SLC22A1. An additive effect with other immunosuppressants cannot be excluded.
The substance is quickly absorbed from the gut with an absolute bioavailability of 79%. It reaches highest blood plasma levels after about an hour; in different individuals the time to reach this level ranges from 0.5 to 3 hours. Food intake has no relevant influence on the drug's pharmacokinetics. 50% of the circulating baricitinib are bound to blood plasma proteins. Less than 10% of the substance is metabolized to four different oxidation products by CYP3A4; the rest is left unchanged. Elimination half-life is 12.5 hours on average. About 75% is eliminated via the urine, and 20% via the faeces.
History
Clinical trials
31 clinical trials had been registered for baricitinib of which 24 had completed, and 4 of 6 phase 3 trials had completed. In April 2020, Lilly announced they were investigating the use of baricitinib for treating COVID-19 patients. The drug's anti-inflammatory activity is expected to act on the inflammatory cascade associated with COVID-19.
Approval process
In January 2016, Eli Lilly submitted a new drug application to the US FDA for the approval of baricitinib to treat moderately-to-severely active rheumatoid arthritis. In December 2016, the European Committee for Medicinal Products for Human Use recommended the approval of baricitinib as a therapy for RA. European approval was granted in February 2017. Despite widespread expectations that the FDA would approve baricitinib for RA, in April 2017, the FDA issued a rejection, citing concerns about dosing and safety. In May 2018, baricitinib was approved in the United States for the treatment of rheumatoid arthritis. In March 2020, the US FDA granted breakthrough therapy designation to baricitinib for the treatment of alopecia areata.
Brand names
In Bangladesh the drug is sold under the trade name Baricinix and Baricent among others.
