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.

Olumiant is supplied as a tablet for oral 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 Results

FDA Approval

The FDA approval of Olumiant 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.

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.

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.

Additional Information

For additional information regarding Olumiant or moderate to severe rheumatoid arthritis with inadequete response to TNF antagonist therapies, please visit https://www.olumiant.com/