Products
Janus kinase inhibitors are commercially available in the form of tablets and capsules with different galenics.
Structure and properties
The structure of Janus kinase inhibitors is characterized by nitrogen heterocycles, which are often condensed.
Effects
The agents have selective immunosuppressive, anti-inflammatory, and antiproliferative properties. The effects are based on inhibition of Janus kinases (JAK). These are intracellular enzymes that belong to the group of tyrosine kinases and transfer phosphate groups. They are involved in signal transduction from the cell membrane to the nucleus and have an influence on gene expression. Four members of the JAK family are distinguished: JAK1, JAK2, JAK3 and TYK2. The active substances have different selectivities. Cytokines such as the interleukins and interferons as well as growth factors bind to their receptor on the cell surface. The singal is further directed to the nucleus by the Janus kinases and the phosphorylated STAT proteins (STAT: Signal Transducers and Activators of Transcription). Excessive activity of mutant JAK2 kinases is involved in the development of myelofibrosis and polycythaemia vera.
Indications
Currently, the best-known indication for Janus kinase inhibitors is rheumatoid arthritis. Other indications exist:
- Psoriatic arthritis
- Inflammatory bowel diseases, ulcerative colitis
- Myelofibrosis, polycythaemia vera
- Allergic dermatitis, atopic dermatitis (veterinary drugs).
Other approvals in the field of autoimmune diseases will follow in the coming years.
Dosage
According to the SmPC. Tablets are usually taken once or twice daily, depending on the drug. Unlike biologics such as TNF-alpha inhibitors, no injection or infusion is required and the dosing interval is shorter. JAK inhibitors do not need to be stored in the refrigerator.
Agents
Approved drugs:
- Baricitinib (Olumiant)
- Fedratinib (Inrebic)
- Ruxolitinib (Jakavi)
- Tofacitinib (Xeljanz)
- Upadacitinib (Rinvoq)
Other agents:
- Oclacitinib (Apoquel) – veterinary drug product.
The drug group is in development and several compounds are in the pipeline.
Contraindications
Full precautions can be found in the drug label.
Interactions
Many Janus kinase inhibitors are substrates of CYP450 isozymes, and interactions with CYP inhibitors and inducers are possible. Immunosuppressants may increase adverse effects.
Adverse effects
The most common possible adverse effects include:
- Upper respiratory tract infections, cough, fever.
- Gastrointestinal disorders such as nausea and diarrhea.
- Blood count disorders, because EPO (erythropoietin) is also active via jannus kinases.
- Central nervous disorders: Dizziness, headache
Due to immunosuppressive properties, the drugs may promote the occurrence of infectious diseases and cancers.
