JAK-inhibitor (Baricitinib)

Infectious diseases
NHS Lothian

Baricitinib (Olumiant®) is a selective and reversible Janus kinase (JAK) 1 and 2 inhibitor, licensed as an anti-inflammatory treatment for rheumatoid arthritis and atopic dermatitis. JAK-inhibitors are thought to control high levels of cytokines and inflammation, seen in patients with severe SARS-CoV-2 infection. Results from the RECOVERY trial demonstrate that baricitinib reduces the risk of death when given to hospitalised patients with severe COVID-19.

Baricitinib can be considered in children (age 2 to 17 years inclusive) with severe COVID-19. However, this guidance only covers the use in adult patients. Any use in children should be discussed with paediatrics.

 

Co-administration

Use of baricitinib in the treatment of COVID-19 should be considered as ‘additive’ to the use of an IL-6 inhibitor (tocilizumab or sarilumab), rather than an alternative. In other words, a patient may be given an IL-6 inhibitor after treatment with baricitinib has been commenced (or vice versa), according to clinical judgement.

Baricitinib may be administered in combination with IL-6 receptor blockers (as well as corticosteroids, unless contraindicated), according to clinical judgement, in patients with severe or critical COVID-19. If an IL-6 inhibitor is not deemed suitable, or eligibility criteria (for an IL-6 inhibitor) are unmet, baricitinib treatment may still be considered.

Eligibility criteria

Patients must meet all the eligibility criteria and none of the exclusion criteria. Patients hospitalised due to COVID-19 are eligible to be considered for baricitinib if the following criteria are met:

  • COVID-19 infection is confirmed by microbiological testing or where a multi-disciplinary team has a high level of confidence that the clinical and/or radiological features suggest that COVID-19 is the most likely diagnosis;

AND

  • Viral pneumonia syndrome is present;

AND

  • Aged 2 years and over;

AND

  • Receiving supplemental oxygen or respiratory support* for the treatment of COVID-19;

AND

  • Receiving dexamethasone or an equivalent corticosteroid unless contraindicated.

*Defined as: high-flow nasal oxygen, continuous positive airway pressure (CPAP) or non-invasive ventilation, or invasive mechanical ventilation.

Exclusion criteria and cautions

Baricitinib should not be administered in the following circumstances:

  • Known hypersensitivity to baricitinib;
  • eGFR <15 ml/min/1.73m2 (adult patients)
  • Receiving dialysis or haemofiltration;
  • Absolute neutrophil count (ANC) less than 0.5 x 109 cells/L;
  • Active tuberculosis;
  • Pregnancy or breastfeeding.

The summary of Product Characteristics (SmPC) for baricitinib also advises caution in severe hepatic impairment.

Please refer to Summary of Product Characteristics (SmPC) for baricitinib.

 

Pregnancy / women of childbearing potential and breastfeeding

Baricitinib should not be used during pregnancy.

For women who are breast-feeding, the SmPC for baricitinib states:

“It is unknown whether baricitinib/metabolites are excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown excretion of baricitinib in milk. A risk to newborns/infants cannot be excluded and Olumiant [baricitinib] should not be used during breast-feeding. A decision must be made whether to discontinue breast-feeding or to discontinue Olumiant [baricitinib] therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.”

 

Dose and administration

The use of baricitinib in COVID-19 is off label.

The recommended dose of baricitinib is 4mg once daily for 10 days (or until discharge if sooner). The dose should be halved to 2mg once daily in the following circumstances:

  • eGFR 30 to <60 mL/min/1.73m2
  • Co-administration of an Organic Anion Transporter 3 (OAT3) inhibitor with a strong inhibition potential, such as probenecid.

The dose should be reduced further to 2mg on alternate days in the following circumstances:

  • eGFR 15 to <30 mL/min/1.73m2

Dosing of baricitinib has not been studied for an eGFR <30 mL/min/1.73m2 and clinical judgement should be exercised prior to prescribing.

Baricitinib should be taken with or without food and may be taken at any time. Seek advice from pharmacist if patient requires NG or PEG tube administration.

Individuals who are being considered for treatment under this policy, who are already taking baricitinib for a licenced indication at the dose of 4mg per day, should not receive additional baricitinib doses. However, if such individuals are already taking baricitinib at a dose of 2mg per day, the dose may be increased for the recommended treatment interval as described in these guidelines provided all eligibility criteria are met and provided the increased dose is deemed clinically appropriate (which includes the patient not being within the dose reduction categories described).

 

Documentation of approved use

The use of baricitinib for the indication of COVID-19 pneumonitis in NHSL requires documentation on Trak using a specific shortcode. It is important that the shortcode (see below) is used as pharmacy will monitor use through a BOXI report which requires this particular shortcode. Weekly allocations to NHSL are provided based on usage.

  • The consultant in charge of the patient should:
    • Check the patient meets the JAK-inhibitor therapy approval criteria as detailed above.
    • Where possible gain the agreement of the patient to use this medicine.
  • The consultant in charge of the patient is responsible for:
    • Documenting the use of baricitinib in the patient’s TRAK notes using the following short code: \baricov
    • Reporting any adverse drug reactions on the COVID-19 yellow card reporting site. https://coronavirus-yellowcard.mhra.gov.uk/
  • Important! With the exception of critical care areas, baricitinib will only be supplied by pharmacy 9am to 4pm (Mon to Fri) and during pharmacy opening-hours at weekends, which vary across the acute hospitals. Out of hours requests from non-critical care areas will not be processed until the following morning unless an urgent supply is requested by the ID consultant on call.
  • Pharmacy staff will check Trak documentation by accessing the completed shortcode entry on TRAK (this will also inform stock holding).

It is vital that any serious suspected adverse reactions are reported directly to the MHRA via the new dedicated COVID-19 Yellow Card reporting site at: https://coronavirus- yellowcard.mhra.gov.uk/.

Treatment with baricitinib can lower the ability of the immune system to fight infections. This could increase the risk of getting a new infection or make any infection the patient contracts worse. All handovers of clinical care (including between hospitals if patients are transferred, between levels of care and clinical teams within hospitals, and between hospitals and primary care) must explicitly mention that baricitinib has been given and the date of administration. Clinicians must ensure the GP is aware the patient has received baricitinib and should provide information to the patient to such effect.

TRAK shortcode

\BARICOV

This is the Trak short code to be used to document the use of Baricitinib.