From the Guidelines
Drugs targeting gamma interferon, such as JAK inhibitors and emapalumab, are effective in reducing inflammation and improving outcomes in conditions like macrophage activation syndrome (MAS) and Still's disease, with emapalumab showing a high rate of complete response (>90%) in patients who have failed high-dose GCs 1.
Mechanism of Action
These medications work by interrupting the inflammatory cascade initiated by gamma interferon, which normally activates macrophages and increases MHC class II expression. By dampening this pathway, these drugs reduce the inflammatory response that drives tissue damage in autoimmune diseases.
Treatment Options
Some of the key treatment options include:
- JAK inhibitors like tofacitinib, baricitinib, and upadacitinib, which block the signaling pathway activated by gamma interferon
- Emapalumab, a monoclonal antibody that directly binds to and neutralizes gamma interferon, used specifically for hemophagocytic lymphohistiocytosis
Dosing and Monitoring
Typical dosing for these medications varies, with tofacitinib typically given at 5mg twice daily, baricitinib at 2-4mg once daily, and upadacitinib at 15mg once daily. Emapalumab is given at 1mg/kg twice weekly. Treatment is usually long-term with regular monitoring of blood counts, liver function, and lipid profiles every 3-6 months. Patients should be screened for tuberculosis before starting therapy, as JAK inhibitors can increase infection risk 1.
Real-World Evidence
Real-world data provide the rationale for early initiation of IL-1 or IL-6i in patients with a new onset of sJIA/AOSD, with high rates of high-level response in a short time frame (a few months), associated with rapid tapering and withdrawal of GCs 1.
Safety Considerations
Safety data from trials are limited, but a pooled analysis of the safety data provided by clinical trials, their open-label extension phase, and the registries allowed the collection of data from more than 1000 PY of exposure to IL-1i or IL-6i in sJIA/AOSD, showing that SAEs were more frequent in patients receiving IL-6i, and the lowest rate of infectious AEs was observed with anakinra, the IL-1i with a short half-life 1.
From the Research
Drugs Targeting Gamma Interferon
- Gamma interferon (IFN-γ) is a cytokine that plays a crucial role in the immune system, and its dysregulation is implicated in various autoimmune and inflammatory diseases 2, 3.
- Janus kinase (JAK) inhibitors are a class of drugs that target the JAK-signal transducer and activator of transcription (STAT) pathway, which is involved in the signaling of various cytokines, including IFN-γ 4, 5, 2.
- JAK inhibitors have been shown to be effective in the treatment of various autoimmune and inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis 4, 5, 2, 6.
- In the context of vitiligo, a skin disorder characterized by the destruction of melanocytes, JAK inhibitors have been shown to be effective in targeting the IFN-γ-chemokine signaling axis, which is implicated in the pathogenesis of the disease 3.
- Specific JAK inhibitors, such as tofacitinib, baricitinib, and ruxolitinib, have been approved for the treatment of various autoimmune and inflammatory diseases, and are being evaluated for their potential use in other conditions 4, 5, 6, 3.