Baricitinib and Tofacitinib
The information provided below is for readers based in the United States of America. Readers outside of the United States of America should seek the information from local sources.
Background and Overview
Baricitinib and tofacitinib belong to a family of drugs called janus kinase (JAK) inhibitors, which are a group of drugs primarily used to treat long-term inflammatory diseases, such as rheumatoid arthritis. JAK inhibitors are also used in certain patients who have COVID-19.
In the United States, the ability to use JAK inhibitors, and specifically baricitinib and tofacitinib, to treat COVID-19 is granted under emergency use authorization (EUA) of the US Food and Drug Administration (FDA). In people with COVID-19, each of these medicines can be given when the disease progresses to a point where the patient requires supplemental or low flow oxygen delivered through either a tube in the nose or through a simple face mask.
Baricitinib and tofacitinib are also used when COVID-19 has reached a point that the patient requires high flow oxygen, or oxygen that is delivered through other devices, such as a non-rebreather mask, a high flow nasal cannula, or a CPAP machine.
Treating a patient with COVID-19 with baricitinib or tofacitinib is typically reserved for situations where there is a shortage of another drug, called tocilizumab.
Appropriate Patients for Baricitinib and Tofacitinib
Baricitinib and tofacitinib are specifically used to overcome cytokine release syndrome (CRS). CRS is one of the leading abnormalities of COVID-19 and is responsible for causing a life-threatening condition associated with severe COVID-19 called acute respiratory distress syndrome (ARDS).
CRS typically involves an immune chemical called interleukin 6 (IL-6). While tocilizumab works directly against IL-6, baricitinib and tofacitinib both interrupt the processes that produce IL-6 and other interleukin chemicals.
Since doctors know more about tocilizumuab, they generally prefer to use it more often than either baricitnib or tofacitnib when treating COVID-19. In general, doctors have been using JAK inhibitors with increasing frequency in patients who are not on mechanical ventilation. Considering baricitinib and tofacitinib are administered orally, they tend not to be used for this purpose.
A patient receiving baricitinib or tofacitinib for COVID-19 would do so while also receiving a series of other medications. At minimum, a patient being treated for COVID-19 would generally also receive a corticosteroid, like dexamethasone. In addition, patients with COVID-19 may also receive the antiviral drug remdesivir, medication that works against blood clotting, as well as a number of other medications.
Pregnancy and Lactation Issues
There are very few data reflecting the use of baricitinib or tofacitinib for COVID-19 during pregnancy and lactation. Studies on laboratory animals suggest that both of these medicines can cross the placenta and reach the fetal blood and also can enter breastmilk. Considering these studies involved very high doses of these medications, additional information from human study is required.
The dosages of baricitinib and/or tofacitinib appropriate for treating COVID-19 create concentrations of the medicines in the blood at much lower than the concentrations observed in the laboratory animal studies previously mentioned.
Considering that pregnant women are at high risk for severe COVID-19, and that COVID-19 in the mother, even when mild, puts the fetus in danger, the benefit-to-risk tradeoff is likely to weigh in favor of using the drug when treating pregnant women with COVID-19.
How Baricitinib and Tofacitinib are Administered
Baricitinib and tofacitinib are both oral medications, meaning that they are taken in pill form.
Adverse Effects Associated with Baricitinib and Tofacitinib
Adverse effects reported for these drugs result mostly from suppression of immune function, including infections, shingles, and suppression of bone marrow; elevations in the level of certain liver enzymes have also been reported. In rare cases, perforation of the gastrointestinal tract has been reported.
Importantly, these unintended effects have been reported in connection with long-term use of the drugs, such as when used for treating rheumatoid arthritis. In sharp contrast, baricitinib and tofacitinib, when used for treating COVID-19, are only used on a very short-term basis.
References
National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. Retrieved January 2, 2021
Quek E, Tahir H, Kumar P, Hastings R, Jha R. Treatment of COVID-19: a review of current and prospective pharmacotherapies. Br J Hosp Med (Lond). 2021 Mar 2;82(3):1-9. doi: 10.12968/hmed.2021.0112. Epub 2021 Mar 12. PMID: 33792391.
US Food and Drug Administration. Fact sheet for healthcare providers: emergency use authorization (EUA) of baricitinib. Accessed January 2, 2021