Over the last 2 decades, JAK inhibitors have emerged as a powerful tool for treating autoimmune diseases. The field is still evolving, with researchers looking for ways to improve efficacy and safety.
- Early 2000’s: Researchers began unraveling the role of Janus Kinase (JAK) enzymes in the immune system. JAKs play a critical role in signaling pathways triggered by cytokines.
- First Generation (2010s): This period marked a major breakthrough.
- 2011: The FDA approves ruxolitinib, the first JAK inhibitor, for myeloproliferative disorders.
- 2012: Tofacitinib, another JAK inhibitor, gains FDA approval for rheumatoid arthritis. This ushers in a new era for treating autoimmune diseases.
- Expanding Applications: Since the initial approvals, JAK inhibitors have shown promise in treating various autoimmune conditions, including:
- Psoriasis
- Inflammatory bowel disease
- Atopic dermatitis
- Alopecia areata
- Plaque Psoriasis
- Continued Development: Research is ongoing to:
- Develop more specific JAK inhibitors targeting individual JAK enzymes. This could minimize side effects while maximizing therapeutic effects for specific diseases.
- Explore the use of JAK inhibitors in combination with other therapies for a more comprehensive approach.
Some Publications: JAKs in Myositis:
- Various case studies have been published
- Published in 2020, High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle. Of the thousands tested, several broad classes of drugs were identified including inhibitors to JAKs, HDACs, CDKs, HIF1, and DNA topoisomerase II. Some of the most promising drugs, which are JAK and HDAC inhibitors https://pubmed.ncbi.nlm.nih.gov/32459468/
- Published in 2021, This open-label 12-week study was conducted to evaluate the efficacy and safety of tofacitinib in active, treatment-refractory dermatomyositis. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084900/
- Recent meta-analysis demonstrates the efficacy and safety of JAK inhibitors in patients with DM/PM, providing evidence for its future clinical application. Nevertheless, due to a small amount of data, confirmation of this conclusion requires more RCTs. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1382728/full
The Use of JAK Inhibitors in Dermatomyositis and Juvenile Myositis by Stacey Tarvin, MD, MS, FAAP, FACR, University of Indiana School of Medicine, USA, Co-Chair, CARRA JDM Working Group, chair, Cure JM Clinical Care Network.
About this session:
Hear from Dr. Stacey Tarvin about the use of JAK inhibitors in JDM and the potential efficacy of JAK inhibitors, such as tofacitinib and baricitinib, in improving muscle strength and skin symptoms in patients.
About Dr. Stacey Tarvin:
Dr. Tarvin is an Assistant Professor of Clinical Pediatrics at Riley Hospital for Children and Indiana University School of Medicine. She is the Vice Chair of the CARRA JDM Research Committee and Co-Lead of the CARRA JDM Therapeutics group, as well as a member of the PReS JDM working party.
She leads Clinical Research efforts in her division, including PI for pharma trials, registry studies, and investigator-initiated projects. Her focus is on therapeutics, consensus treatment plans, and telehealth in JDM. She is the Chair of Cure JM’s Clinical Care Network.
The Potential of JAKs in Fighting JM by Julie Park, MD, MHS, Johns Hopkins Rheumatology.
In Cure JM’s June 2024, “Ask the Doc” Town Hall, Dr. Julie Paik joins in a Q&A session to shed light on what JAK inhibitors are, how they work in JM, when parents might consider discussing JAKs as a treatment option, and the pros and cons of their use.
Dr. Paik has experience in testing and using JAKs in JM and other rheumatic conditions with success and has published some early case studies to usher in their use. As JAKs become an increasing treatment option, you’ll gain valuable insight on important considerations regardless of where you may be on the JM journey.
Session topics include:
- History of JAKs & early use in JM
- Early studies & results in JM
- When to discuss JAK use with your doctor
- Understanding risks vs. benefits
- Future of JAKs – Will they replace other meds like prednisone?
- Q&A session from our families and patients and closing
Introduction to this Topic:
JAK inhibitors are newer treatments being studied and used increasingly off-label* in juvenile myositis at various phases of the disease.
How Do JAKs Work?
The immune system is made up of immune system cells that behave like “soldiers,” protecting the body from invaders like viruses. However, with myositis, these immune system soldiers are misbehaving. They are attacking healthy skin and muscles instead of viruses.
Current myositis treatments (such as steroids and methotrexate) typically work by trying to dampen the immune response, so that the misbehaving soldiers cannot do as much damage to healthy skin and muscle.
JAK inhibitors work by helping to improve the signals going to the misbehaving soldiers. When the soldiers get the right information and are not misbehaving, they are causing less damage.
JAKs That Are Currently Used in JM are:
- Tofacitinib (Xeljanz)
- Ruxolitinib (Jakafi)
- Upadacitinib (Rinvoq)
- Baricitinib (Olumiant)
