Baricitinib 💊

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

Baricitinib is approved for medical use in the European Union and in the United States. An important side effect of JAK inhibitors is serious bacterial, mycobacterial, fungal and viral infections.

Mechanism of action

Baricitinib is a Janus kinase (JAK) inhibitor that reversibly inhibits Janus kinase 1 with a half maximal inhibitory concentration (IC50) of 5.9 nM and Janus kinase 2 with an IC50 of 5.7 nM. Tyrosine kinase 2, which belongs to the same enzyme family, is affected less (IC50 = 53 nM), and Janus kinase 3 far less (IC50 > 400 nM). Via a signal transduction pathway involving STAT proteins, this ultimately modulates gene expression in immunological cells. Other JAK inhibitors include tofacitinib, which is indicated for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis; fedratinib, and ruxolitinib.

Pharmacokinetics

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.

Side effects

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

効能

  • 既存治療で効果不十分な関節リウマチ(関節の構造的損傷の防止を含む)
  • アトピー性皮膚炎(最適使用推進ガイドライン対象)
  • SARS-CoV-2による肺炎(ただし、酸素吸入を要する患者に限る)
  • 円形脱毛症(ただし、脱毛部位が広範囲に及ぶ難治の場合に限る)

禁忌

  • 各適応症共通
    • 本剤への過敏症の既往歴がある患者
    • 活動性結核の患者
    • 好中球数が500/mm3未満の患者
    • 妊婦又は妊娠している可能性のある女性
  • 関節リウマチ、アトピー性皮膚炎、円形脱毛症
    • 重篤な感染症(敗血症等)の患者
    • 重度の腎機能障害を有する患者(eGFRが30未満)
    • リンパ球数が500/mm3未満の患者
      -ヘモグロビン値が8g/dL未満の患者
  • SARS-COV-2による肺炎
    • 透析患者又は末期腎不全(eGFRが15未満)
    • リンパ球数が200/mm3未満の患者

COVID-19

2020年11月、FDAはバリシチニブとレムデシビルの併用療法について、補助酸素、侵襲的機械式人工呼吸、または体外式膜酸素供給（ECMO）を必要とする2歳以上の入院患者におけるCOVID-19の疑いまたは検査で確認されたCOVID-19の治療のための緊急使用許可（EUA）を発行した。

2021年4月23日、日本でSARS-CoV-2による肺炎の治療薬としてバリシチニブが承認された。