OLUMIANT 2 mg

Indications

• Moderate-to-severe active rheumatoid arthritis
• Moderate-to-severe atopic eczema
• Active psoriatic arthritis
• Moderately to severely active ulcerative colitis
• Active Crohn’s disease

Dosage

Adults: For adults aged 18–74 years, the recommended dosage is 4 mg once daily. For adults aged 75 years and over, the dosage is 2 mg once daily. Dose adjustments may be necessary based on treatment interruptions due to side effects or history of infections.

Mechanism of action

Baricitinib acts by selectively inhibiting JAK1 and JAK2, which are intracellular enzymes that mediate signaling from cytokines and growth factor receptors. This inhibition disrupts the JAK-STAT signaling pathway, leading to reduced transcription of inflammatory mediators involved in autoimmune responses, such as interleukins and interferons. By decreasing the activity of these pathways, baricitinib effectively reduces inflammation and modulates immune responses.

Pharmacodynamics

As a DMARD, baricitinib has been shown to significantly reduce inflammation in animal models of arthritis, preserving cartilage and bone without adversely affecting humoral immunity. It decreases levels of immunoglobulins and serum C-reactive protein, which are markers of inflammation in patients with rheumatoid arthritis. These effects contribute to the alleviation of symptoms and the slowing of disease progression.

Pharmacokinetics

Baricitinib is administered orally and exhibits a half-life of approximately 12 hours. It is primarily metabolized by the liver, with a significant portion excreted through the kidneys. The drug's pharmacokinetics can be influenced by other medications, particularly those that affect liver enzymes or renal function. Therefore, monitoring and potential dose adjustments may be necessary in patients with hepatic or renal impairment.

Contra-indications

• Active tuberculosis
• Severe infections
• History of venous thromboembolism

Adverse effects

• Increased risk of venous thromboembolism
• Exfoliative dermatitis
• Erythrodermic psoriasis
• Infections
• Headache
• Nausea
• Elevated liver enzymes

Interactions

• Filgotinib: Severe (increases risk of immunosuppression)
• Live vaccines: Severe (increases risk of generalized infection, possibly life-threatening)
• Leflunomide: Unknown (increases exposure)
• Teriflunomide: Unknown (increases exposure)

Precautions

• Screen for tuberculosis prior to treatment
• Monitor for signs of infection during treatment
• Use with caution in patients with additional risk factors for venous thromboembolism
• Consider dose adjustments in older adults or those with renal impairment

Pregnancy

Limited data on safety, use only if potential benefit justifies potential risk to the fetus.

Breast-feeding

Unknown if excreted in human milk, use caution and consider benefits versus risks.

Storage

Store at room temperature, protect from moisture and light.

Formulations

• Oral tablets: 2 mg, 4 mg

Mechanism of action

As members of the tyrosine kinase family, Janus kinases (JAKs) are intracellular enzymes that modulate signals from cytokines and growth factor receptors involved in hematopoiesis, inflammation, and immune cell function. Upon binding of extracellular cytokines and growth factors, JAKs phosphorylate and activate Signal Transducers and Activators of Transcription (STATs). STATs modulate intracellular activity, including gene transcription of inflammatory mediators that promote an autoimmune response, such as IL-2, IL-6, IL-12, IL-15, IL-23, IFN-γ, GM-CSF, and interferons. The JAK-STAT pathway has been implicated in the pathophysiology of rheumatoid arthritis, as it is associated with an overproduction of inflammatory mediators. There are four JAK proteins: JAK 1, JAK 2, JAK 3 and TYK2. JAKs form homodimers or heterodimers and pair differently in different cell receptors to transmit cytokine signaling. Baricitinib is a selective and reversible inhibitor of JAK1 and JAK2 with less affinity for JAK3 and TYK2; however, the relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known. Baricitinib inhibits the activity of JAK proteins and modulates the signaling pathway of various interleukins, interferons, and growth factors. It was also shown to decrease the proliferation of JAK1/JAK2 expression in mutated cells and induce cell apoptosis.

Pharmacodynamics

Baricitinib is a disease-modifying antirheumatic drug (DMARD) used to ameliorate symptoms and slow down the progression of rheumatoid arthritis. In animal models of inflammatory arthritis, baricitinib was shown to have significant anti-inflammatory effects but also led to the preservation of cartilage and bone, with no detectable suppression of humoral immunity or adverse hematologic effects. Baricitinib decreased the levels of immunoglobulins and serum C-reactive protein in patients with rheumatoid arthritis.