Olumiant (baricitinib) - 3 Indications

Scroll down for more information on each indication:

• for the treatment of adult patients with moderately to severely active rheumatoid arthritis; approved May of 2018
• for the treatment of COVID-19 in hospitalized adults; approved May of 2022
• for the treatment of severe alopecia areata; approved June of 2022

General Information

Olumiant (baricitinib) is a Janus kinase (JAK) inhibitor.

Olumiant is specifically indicated for:

• the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies
• for the treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) 
• for the treatment of adult patients with severe alopecia areata

Olumiant is supplied as a tablet for oral administration. Scroll down for recommended dosing/administration for each indication.

Mechanism of Action

Olumiant (baricitinib) is a Janus kinase (JAK) inhibitor. JAKs are intracellular enzymes which transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoiesis and immune cell function. Within the signaling pathway, JAKs phosphorylate and activate Signal Transducers and Activators of Transcription (STATs) which modulate intracellular activity including gene expression. Baricitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs.

JAK enzymes transmit cytokine signaling through their pairing. In cell-free isolated enzyme assays, baricitinib had greater inhibitory potency at JAK1, JAK2 and TYK2 relative to JAK3. In human leukocytes, baricitinib inhibited cytokine induced STAT phosphorylation mediated by JAK1/JAK2, JAK1/JAK3, JAK1/TYK2, or JAK2/TYK2 with comparable potencies. However, the relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.

Side Effects

Adverse effects associated with the use of Olumiant may include, but are not limited to, the following:

• upper respiratory tract infections
• nausea
• herpes simplex
• herpes zoster

The Olumiant drug label comes with the following Black Box Warning:

Serious Infections: Patients treated with Olumiant are at risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt Olumiant until the infection is controlled. Reported infections include:

• Active tuberculosis (TB), which may present with pulmonary or extrapulmonary disease. Test patients for latent TB before initiating Olumiant and during therapy. Treatment for latent infection should be considered prior to Olumiant use.
• Invasive fungal infections, including candidiasis and pneumocystosis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
• Bacterial, viral, and other infections due to opportunistic pathogens.

Carefully consider the risks and benefits of Olumiant prior to initiating therapy in patients with chronic or recurrent infection.

Closely monitor patients for the development of signs and symptoms of infection during and after treatment with Olumiant, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

Malignancies: Lymphoma and other malignancies have been observed in patients treated with Olumiant.

Thrombosis: Thrombosis, including deep venous thrombosis (DVT) and pulmonary embolism (PE), has been observed at an increased incidence in patients treated with Olumiant compared to placebo. In addition, there were cases of arterial thrombosis. Many of these adverse events were serious and some resulted in death. Patients with symptoms of thrombosis should be promptly evaluated.

Indication 1 - for the treatment of rheumatoid arthritis

approved May of 2018

Dosing/Administration

The recommended dose is 2 mg once daily. Olumiant may be used as monotherapy or in combination with methotrexate or other DMARDs. Olumiant is given orally with or without food.

Olumiant initiation is not recommended in patients with an absolute lymphocyte count (ALC) less than 500 cells/mm3, absolute neutrophil count (ANC) less than 1000 cells/mm3, or hemoglobin level less than 8 g/dL. Avoid use of Olumiant in patients with active, serious infection, including localized infections. Prior to initiating Olumiant, test patients for latent tuberculosis (TB). If positive, consider treating for TB prior to Olumiant.

Clinical Trial Results

The FDA approval of Olumiant for RA was based on two dose-ranging trials and two confirmatory phase 3 trials.

Dose-ranging Trials

The dose-ranging studies I and II included a 12-week randomized comparison of baricitinib 1, 2, 4, and 8 mg versus placebo in 301 and 145 patients, respectively. In dose-ranging Study I, the observed ACR response was similar for baricitinib 1 and 2 mg daily and for baricitinib 4 and 8 mg daily, with the highest response for baricitinib 8 mg daily. In dose-ranging Study II, there was not a clear trend of dose response, with similar response rates for 1 mg and 4 mg and 2 mg and 8 mg.

Confirmatory Trials

The efficacy and safety of Olumiant 2 mg once daily was assessed in two confirmatory phase 3 trials. These trials were randomized, double-blind, multicenter studies in patients with active rheumatoid arthritis diagnosed according to American College of Rheumatology (ACR)/European League Against Rheumatism 2010 criteria. Patients over 18 years of age were eligible if at least 6 tender and 6 swollen joints were present at baseline. The two studies (Studies III and IV) evaluated Olumiant 2 mg and baricitinib 4 mg.

Study III was a 24-week trial in 684 patients with moderately to severely active rheumatoid arthritis who had an inadequate response or intolerance to conventional DMARDs (cDMARDs). Patients received Olumiant 2 mg or 4 mg once daily or placebo added to existing background cDMARD treatment. From Week 16, non-responding patients could be rescued to receive baricitinib 4 mg once daily. The primary endpoint was the proportion of patients who achieved an ACR20 response at Week 12. ACR20 was reached by 39% in the placebo arm and 66% in the Olumiant 2 mg/day arm at Week 12.

Study IV was a 24-week trial in 527 patients with moderately to severely active rheumatoid arthritis who had an inadequate response or intolerance to 1 or more TNF inhibitor therapies with or without other biologic DMARDs (TNFi-IR). Patients received Olumiant 2 mg or baricitinib 4 mg once daily or placebo added to background cDMARD treatment. From Week 16, non-responding patients could be rescued to receive baricitinib 4 mg once daily. The primary endpoint was the proportion of patients who achieved an ACR20 response at Week 12. ACR20 was reached by 27% in the placebo arm and 49% in the Olumiant 2 mg/day arm at Week 12.

Indication 2 -  for the treatment of COVID-19 in hospitalized adults

approved May of 2022

Dosing/Administration

The recommended dose is 4-mg once daily for 14 days or until hospital discharge, whichever comes first.

Clinical Trial Results

The FDA's approval is supported by results from two randomized, double-blind, placebo-controlled Phase 3 studies (ACTT-2 and COV-BARRIER, including the COV-BARRIER OS 7 addendum study).

ACTT-2 was a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults (n=1,033) with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15. Patients receiving baricitinib had a median time to recovery of 7 days compared with 8 days with control and a 30% higher odds of improvement in clinical status at day 15. Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control . The 28-day mortality was 5.1% in the combination group and 7.8% in the control group.

COV-BARRIER was a  double-blind, randomized, placebo-controlled trial and participants (n=1,525) were enrolled from 101 centers across 12 countries in Asia, Europe, North America, and South America. Hospitalised adults with COVID-19 receiving standard of care were randomly assigned (1:1) to receive once-daily baricitinib (4 mg) or matched placebo for up to 14 days. Overall, 27·8% of participants receiving baricitinib and 30·5% receiving placebo progressed to meet the primary endpoint. The 28-day all-cause mortality was 8% (n=62) for baricitinib and 13% (n=100) for placebo, a 38·2% relative reduction in mortality; one additional death was prevented per 20 baricitinib-treated participants. The 60-day all-cause mortality was 10% (n=79) for baricitinib and 15% (n=116) for placebo.

Indication 3 - for the treatment of adults with severe alopecia areata

Dosage/Administration

The recommended dose is 2 mg once daily orally, with or without food. Increase to 4 mg once daily if the response to treatment is not adequate.

For patients with nearly complete or complete scalp hair loss, with or without substantial eyelash or eyebrow hair loss, consider treating with 4 mg once daily, with or without food.

Once patients achieve an adequate response to treatment with 4 mg, decrease the dosage to 2 mg once daily

Clinical Trial Results

The FDA approval was based on two randomized, double-blind, placebo-controlled trials (Trial AA-1 and Trial AA-2) with patients who had at least 50% scalp hair loss as measured by the Severity of Alopecia Tool for more than six months. Patients in these trials received either a placebo, 2 milligrams of Olumiant, or 4 milligrams of Olumiant every day. The primary measurement of efficacy for both trials was the proportion of patients who achieved at least 80% scalp hair coverage at week 36.

In Trial AA-1, 22% of the 184 patients who received 2 milligrams of Olumiant and 35% of the 281 patients who received 4 milligrams of Olumiant achieved adequate scalp hair coverage, compared to 5% of the 189 patients who received a placebo. In Trial AA-2, 17% of the 156 patients who received 2 milligrams of Olumiant and 32% of the 234 patients who received 4 milligrams of Olumiant achieved adequate scalp hair coverage, compared to 3% of the 156 patients who received a placebo.