Clinical Overview: Baricitinib (Olumiant) for Rheumatoid Arthritis, COVID-19

Baricitinib (Olumiant) is a Janus kinase (JAK) inhibitor indicated for the treatment of rheumatoid arthritis (RA) and COVID-19 in hospitalized adults requiring supplemental oxygen, noninvasive or invasive ventilation, or extracorporeal membrane oxygenation (ECMO).¹

A study enrolled 684 patients with RA who had inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drugs (DMARDs) but were naïve to biologic DMARDs. The researchers randomly assigned study participants 1:1:1 to either receive a placebo, a 2 mg dose, or 4 mg dose of baricitinib with the primary endpoint measure being achievement of ACR20.

This is a standardized score created by the American College of Rheumatology to measure the response and efficacy of RA treatment. Reaching ACR20 means that the patient has achieved a 20% improvement in the severity of their RA symptoms.²

At 12 weeks of patients receiving baricitinib 2 mg and 4 mg, 66% and 62% achieved ACR20, with only 39% of the patients reaching the same endpoint with placebo. At 24 weeks, the rates for the placebo, 2 mg, and 4 mg dosage were 42%, 61%, and 65%, respectively.³

The European Union approved both the 2 mg and 4 mg dosages in early 2017. When baricitinib reached American markets in 2018, the FDA approved only the 2 mg, dosage citing the primary reason as the increased risk of thrombosis associated with the 4 mg dosing.⁴

In a subsequent randomized study, researchers evaluated the effects of treatment with baricitinib plus remdesivir on time to recovery and clinical status in 1033 patients, with 515 administered combination therapy and 518 administered remdesivir monotherapy. Patients receiving combination therapy had faster time to recovery, with a median time of 7 days compared to the control group’s time of 8 days.

This difference in recovery was even greater in patients receiving high flow oxygen. Median recovery time in this group was 10 days while patients in the control had a time of 18 days.

Patients receiving baricitinib also displayed lower 28-day mortality compared to the remdesivir monotherapy control group, at 5.1% and 7.8%, respectively. Incidence of all adverse events (AEs)—ordinary, serious, and fatal—was also lower in the combination therapy cohort. Sixteen percent of patients receiving baricitinib experienced serious AEs compared to 21% in the control population.⁵

In early November 2020, the FDA granted emergency use authorization for the use of baricitinib in treating COVID-19 infection. It recently received full FDA authorization in May 2022.

Mechanism of Action

Baricitinib is a small molecule JAK inhibitor to modulate the immune response via reduction of Signal Transducers and Activators of Transcription (STATs) activation.¹

Dosage¹

• Treatment of RA: Take 2 mg orally once daily.
• Treatment of COVID-19: Take 4 mg orally once daily for 14 days or until hospital discharge, whichever comes first. If patients cannot swallow tablets, alternate administration can be used.

Dose Modifications¹

Rheumatoid Arthritis:

• Patients with ALC <500 cells/microliter: Interrupt baricitinib until ALC ≥500 cells/µL.
• Patients with ANC <1000 cells/microliter: Interrupt treatment until ANC ≥1000 cells/µL.
• Patients with hemoglobin <8 g/deciliter: Interrupt treatment until hemoglobin ≥8 g/dL.
• Patients with moderate renal impairment: 1 mg once daily.
• Patients with severe renal impairment: Not recommended.

COVID-19:

• Patients with ALC <200 cells/microliter: Interrupt baricitinib until ALC ≥200 cells/µL.
• Patients with ANC <500 cells/microliter: Interrupt treatment until ANC ≥500 cells/µL.
• Patients with moderate renal impairment: 2 mg once daily.
• Patients with severe renal impairment: 1 mg once daily.
• Patients with ESRD or on dialysis: Not recommended.

Patients Taking a Strong OAT3 Inhibitor:

• Patients receiving baricitinib 4 mg: Reduce the dose to 2 mg once daily.
• Patients receiving baricitinib 2 mg: Reduce the dose to 1 mg once daily.
• Patients receiving baricitinib 1 mg: Consider discontinuation of OAT3 inhibitor.

AEs

Significant AEs include serious infections, mortality, malignancy, major cardiovascular AEs, thrombosis, gastrointestinal perforations, laboratory abnormalities, and hypersensitivity.

Warnings and Precautions¹

• Prescribers should avoid baricitinib in patients with active, serious infection; patients at risk of thrombosis; and patients with an active tuberculosis (TB) infection.
• Provider should discuss baricitinib’s benefits and risks with patients with a history of TB or who have risk factors for TB infection.
• Reactivation of herpes zoster has been reported. If a patient develops an active episode, prescribers should interrupt therapy until the episode resolves.
• Non-melanoma skin cancers have been reported with baricitinib use, and patients at risk for skin cancer should schedule periodic skin examinations.
• If a patient exhibits clinical features of thrombosis, prescribers should discontinue baricitinib therapy.
• Patients on baricitinib should have routine testing of liver enzymes, lipid levels, ANC, ALC, and hemoglobin to monitor for any abnormalities.
• Patients taking baricitinib should avoid live vaccines.

Pregnancy and Lactation¹

There are insufficient data on the effects of baricitinib in pregnant patients to inform a conclusion on the risk of miscarriage or major birth defects. Patients should discuss with their provider the risks and benefits of starting baricitinib while pregnant.

There are currently no data on the presence of baricitinib in human breast milk. Based on the presence in animal breastmilk, the manufacturer advises that patients treated with baricitinib not breastfeed.

About the Author

Matthew Gall is a 2024 PharmD candidate at the University of Connecticut.

References

1. Olumiant Prescribing Information. Lilly USA Inc.; May 2022.

2. Felson DT, LaValley MP. The ACR20 and defining a threshold for response in rheumatic diseases: too much of a good thing. Arthritis Res Ther. 2014;16(1):101. doi:10.1186/ar4428

3. Dougados M, van der Heijde D, Chen YC, et al. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study [published correction appears in Ann Rheum Dis. 2017;76(9):1634]. Ann Rheum Dis. 2017;76(1):88-95. doi:10.1136/annrheumdis-2016-210094

4. Mogul A, Corsi K, McAuliffe L. Baricitinib: The Second FDA-Approved JAK Inhibitor for the Treatment of Rheumatoid Arthritis. Ann Pharmacother. 2019;53(9):947-953. doi:10.1177/1060028019839650 Accessed May 12, 2022

5. Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19. N Engl J Med. 2021;384(9):795-807. doi:10.1056/NEJMoa2031994