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Baricitinib

Baricitinib, sold under the brand name Olumiant among others, is an immunomodulatory medication used for the treatment of rheumatoid arthritis, alopecia areata, and COVID-19.[7][8][9][10] It acts as an inhibitor of janus kinase (JAK), blocking the subtypes JAK1 and JAK2.[11]

Baricitinib is approved for medical use in the European Union[8] and in the United States.[9][12][10]

Medical uses[edit]

In February 2017, baricitinib was approved for use in the European Union as a second-line therapy for moderate to severe active rheumatoid arthritis in adults, either alone or in combination with methotrexate.[13][8]


In May 2018, the US Food and Drug Administration (FDA) approved baricitinib 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.[12][9][7]


In May 2022, the FDA approved baricitinib for the treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).[7][14][15] baricitinib is the first immunomodulatory treatment for COVID-19 to receive FDA approval.[15]


In the United States, baricitinib is authorized under an emergency use authorization (EUA) for the treatment of COVID-19 in hospitalized people aged 2 to less than 18 years of age who require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation.[14]


In June 2022, the FDA authorized baricitinib for the treatment of severe alopecia areata.[10][16]

Contraindications[edit]

During pregnancy, the use of baricitinib is contraindicated.[2][13]

Side effects[edit]

In studies, upper respiratory tract infections and high blood cholesterol levels (hypercholesterolemia) occurred in more than 10% of participants. Less common side effects included other infections such as herpes zoster, herpes simplex, urinary tract infections, and gastroenteritis.[13]

Interactions[edit]

Being metabolized only to a small extent, the substance has a low potential for interactions. In studies, inhibitors of the liver enzymes CYP3A4, CYP2C19, and CYP2C9, as well as the CYP3A4 inducer rifampicin, 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 (OCT1).[13]


An additive effect with other immunosuppressants cannot be excluded.[13]

History[edit]

Baricitinib was discovered by Incyte and licensed to Eli Lilly.[22]

Society and culture[edit]

Legal status[edit]

In January 2016, Eli Lilly submitted a new drug application to the US Food and Drug Administration (FDA) for the approval of baricitinib to treat moderately-to-severely active rheumatoid arthritis.[23]


In December 2016, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the approval of baricitinib as a therapy for rheumatoid arthritis.[11] European Union approval was granted in February 2017.[8]


Despite widespread expectations that the FDA would approve baricitinib for rheumatoid arthritis,[24] in April 2017, the FDA issued a rejection, citing concerns about dosing and safety.[25][26]


In May 2018, baricitinib was approved in the United States for the treatment of rheumatoid arthritis.[9][12][10]


In March 2020, the US FDA granted breakthrough therapy designation to baricitinib for the treatment of alopecia areata[27] and granted approval in June 2022.[16]


The efficacy and safety of baricitinib in alopecia areata was studied in two randomized, double-blind, placebo-controlled trials (Trial AA-1 and Trial AA-2) with participants who had at least 50% scalp hair loss as measured by the Severity of Alopecia Tool for more than six months.[10] Participants in these trials received either a placebo, 2 milligrams of baricitinib, or 4 milligrams of baricitinib every day.[10] The primary measurement of efficacy for both trials was the proportion of participants who achieved at least 80% scalp hair coverage at week 36.[10]