JAK inhibitors for asthma are currently being studied. Asthma is an inflammatory disease of the airways characterized by intermittent episodes of wheezing, chest tightness and cough. Many of the inflammatory pathways implicated in asthma involve factors that activate the Janus Kinase (JAK). The discovery of the Janus kinases activator of transcription (STAT) signaling pathway was a breakthrough in understanding of cell growth and differentiation.
Janus Kinase inhibitors are under active investigation for immune and inflammatory diseases, and they have demonstrated clinical efficacy in diseases such as rheumatoid arthritis and eczema.
Substantial preclinical data suggest that inhibiting JAK will improve airway inflammation and hyperreactivity in asthma.
JAK inhibitors have the potential to bring in a new therapy of anti-inflammatory treatment in asthma.
There are currently 5 FDA compounds for clinical use that are JAK inhibitors. 2 are for hematologic disorders (ruxolitinib and fedratinib). 3 for use in inflammatory diseases (tofacitinib, baricitinib and upadicitinib). Many are in phase 2/3 studies for a variety of conditions including RA, ulcerative colitits, psoriasis and atopic dermatitis.
Current JAK inhibitors for asthma that are being studied in animal models of lung inflammation are; Tofacitinib, P6, AZD0449, Ruxolitinib, iJak-381, LAS194046, iJAK-001, Tofacitinib. They are being studied with different routes of administration as well.
An important aspect of JAK inhibitors for asthma is balancing their potential efficacy in reducing lung inflammation with safety concerns. Potential concerns are:
- Opportunisitic and respiratory viral infections
- Viral reactiviation
- Malignancy and lymphoproliferative disorders
- Decreased lymphocyte and neutrophil counts
- Lipid profile and cardiovascular disease
- Venous thromboembolism
Janus kinase inhibitors for asthma should be clinically useful for multiple types of asthma. An unmet need is for patients with severe asthma whose disease is poorly controlled despite using high dose inhaled steroids and it would be less expensive that biologics. Because JAK inhibitors have a completely different mechanism of action, they may be particularly effective in individuals with asthma resistant to steroids. Inhaled JAK inhibitors will be studied.