JAK inhibitors

DO YOU KNOW JAK?

One of the most important new treatments that many people in the trichological field are talking about are JAK inhibitors.  As Dr. Brett King, MD, PhD said at the summer 2018 American Academy of Dermatology meeting in Chicago, Illinois, “JAK inhibitors will be a very important — maybe the most important — drug class in dermatology because of their broad applicability across numerous conditions that patients commonly, and uncommonly, present within our clinics.”

With this in mind, I thought it fitting to devote this article explaining what a JAK is and why inhibiting it may help many of our trichological clients.

What does ‘JAK’ stand for and what is it?

JAK is short for “Janus Kinase”.  There are four types of Janus Kinases.

Janus kinases are involved in the process of signaling between cells (known as the JAK-STAT pathway). Cell signaling is important in how cells function and in coordinating important actions of cells.

Immune Disorders.

 Examples of the role of JAK-STAT pathways in cell functions are: the regulation of the immune system, responses to infection, immune responses, and inflammation.  If the regulation of the JAK-STAT pathway is disturbed, immune disorders may result.

For the trichologist, immune disorder conditions include alopecia areata, cicatricial alopecia, atopic dermatitis (a form of itchy eczema) and psoriasis.

What is a JAK inhibitor?

A JAK inhibitor is a substance that inhibits the JAK-STAT pathway, thus potentially reducing the immune disease.

JAK inhibitors target the processes that cause these diseases and, therefore, interrupt those processes to reverse the diseases or make them better.

JAK inhibitors in the news recently are Ruxolitinib and Tofacitinib which were approved by the FDA to treat rheumatoid arthritis and bone marrow disease. Some studies have shown the potential of these medications to also help improve moderate to severe atopic dermatitis and alopecia areata.

Case Reports

1) A sixteen patient study (all with Alopecia Universalis) used two topical JAK inhibitors, 2% tofacitinib and 1% ruxolitinib, for 28 weeks. Five patients (31%) demonstrated partial hair regrowth, two patients (12%) had significant regrowth over their entire scalp and eyebrows (see reference 1).

2) A 22-year-old man presented with a history of Alopecia Universalis (AU) that progressed over 5 years. He exhibited hair loss on the scalp, eyebrows, eyelashes, face, chest, and bilateral upper and lower extremities.  Skin biopsy results of the scalp were consistent with those of AU, which was previously treated with intralesional steroids with minimal improvement.  Because of the lack of response of the AU, the patient was started on off-label tofacitinib (JAK inhibitor) at a dose of 5 mg orally, twice daily. After 10 months of treatment, the patient experienced hair regrowth on all of the affected body parts. After treatment, the patient reported no adverse side-effects (see reference 5).

3) There have also been promising developments in other topical JAK inhibitors studies which have been shown to help patients with alopecia areata. These are currently in Phase II and Phase III trials that are assessing the JAK inhibitors’ efficacy (see reference 3).

Trichological Analysis

Before recommending a JAK inhibitor, I suggest a trichologist send their client/patient to a physician to check blood levels of vitamin D, vitamin B12, ferritin, and thyroid (TSH). 

It is also important to discuss a patient’s lifestyle and medical history such as, stress, diet, medications, family and health history.

Conclusion

Over the years, effective treatment(s) for alopecia areata, atopic dermatitis, etc. have been limited. It is hoped that over the next few years JAK inhibitors will provide a more reliable treatment option.  By working with a dermatologist or immunologist, a trichologist would be giving their clients the best possible supervision to help improve their condition.

Although JAK inhibitors have the potential to help improve certain trichological conditions, further studies are needed on long term safety, best dosages, vehicles used for topical formulations for skin penetration and reduced systemic absorption, and cost.

I hope that by 2020 these questions will have been successfully answered.

References

1) Bokari L, et al.Treatment of alopecia universalis with topical Janus kinase inhibitors – a double blind, placebo, and active controlled pilot study. International Journal of Dermatology, Aug 2018.

2) Gotthardt D, et al. STATs in nK-Cells: The Good, the Bad, and the Ugly. Frontiers in Immunology, 2017; 7: 694.

3) Hosking AE, et al. Topical Janus kinase inhibitors: A review of applications in dermatology. Journal of American Academy Dermatology, 2018; 9: 535-544.

4) Iorizzo M, et al. Emerging drugs for alopecia areata: JAK inhibitors. Expert Opinions on Emerging Drugs,Mar 2018; 23(1): 77-81.

5) Morris GM, et al. Simultaneous improvement of alopecia universalis and atopic dermatitis in a patient treated with a JAK inhibitor. JAAD Case Reports, 2018; 4: 515-517.

6) Rawling JS, et al. The JAK/STAT signaling pathway.Journal of Cell Science, 2004; 117(8): 1281-1283.

7) Seif F, et al. The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells.Cell Communication and Signaling, 2017; 15: 23.

©2018 World Trichology Society       www.WorldTrichologySociety.org