Tofacitinib JAK inhibitor for hair loss

JAK inhibitors, also known as Janus kinase inhibitors or jakinibs are medication developed to stop or decrease the activity of one or several of the Janus kinase family of enzymes. These inhibitors are mainly used to treat a number of conditions that range from inflammatory disease like rheumatoid arthritis to autoimmune diseases and even cancer.

Throughout the testing process, JAK inhibitors have also been effective in treating cases of alopecia areata as well as other types of alopecia. Further studies suggest that JAK inhibitors show huge potential for reversing hair loss, with some medical specialists considering them the “holy grail” of potential treatments. But before delving more into how JAK inhibitors may cure hair loss, let’s take a closer look at how they work.

How they work

researchers have observed that JAK inhibitors played a role in kick-starting enzymes in hair follicles that block hair in the dormant state of growth

JAK enzymes have numerous functions in the body, one of which has to do with the hair growth cycle. JAK inhibitors suppress the function of JAK enzymes, helping with inflammation down to cell level and providing a potential solution for hair loss. JAK inhibitors have been developed as a solution for conditions such as rheumatoid arthritis but have also been used to aid or treat other inflammatory conditions. During trials for rheumatoid arthritis medication, researchers have observed that JAK inhibitors played a role in kick-starting enzymes in hair follicles that block hair in the dormant state of growth. (Shreberk-Hassidim R et al., 2017)

JAK Inhibitors for hair loss

The results were extremely promising with nine out of the twelve patients showing a whopping 92% hair regrowth by the end of the treatment

JAK inhibitors have shown the most promise when it comes to addressing alopecia areata, which is a significant step in the right direction as there is no FDA-approved treatment for the condition. The two drugs that hold most promise in providing relief are ruxolitinib and tofacitinib.

Ruxolitinib

A University of Columbia study (Mackay-Wiggan J. et al, 2016) looked into the effects of the oral JAK1/2 inhibitor ruxolitinib on 12 patients who suffered from moderate to severe cases of alopecia areata. Researchers administered 20mg of the substance, twice per day for a period of 3 to 6 months with an extra 3 months treatment with a follow-up off drug. The results were extremely promising with nine out of the twelve patients showing a whopping 92% hair regrowth by the end of the treatment. While the study’s results were overwhelmingly positive with basically no side-effects, larger, randomized studies are required to precisely determine the efficiency of ruxolitinib in treating alopecia areata.

Tofacitinib

Of the total 66 participants in the study, 32% experienced 50% or greater improvement in hair regrowth

Tofacitinib is another potential drug that aims to treat alopecia areata by using the pan-JAK inhibitor, tofacitinib citrate. A 2-center, open label, single arm trial was carried out by a team of researchers from universities such as Yale, Columbia and Stanford. The study used Tofacitinib 5mg which was administered twice a day for 3 months. Of the total 66 participants in the study, 32% experienced 50% or greater improvement in hair regrowth. The downside of the results showed that while the treatment was efficient, after drug cessation, the disease relapsed in under 9 weeks. Side-effects were minor and consisted of grade I and II infections in a few patients. While the drug was deemed safe and effective, the lack of a durable cure requires further development and testing. (Kennedy Crispin M et al., 2016)

Alopecia universalis is another condition where JAK inhibitors have shown promising results. Alopecia universalis is a rare but devastating condition, an aggravated form of alopecia areata that leads to total loss of hair on the scalp and body. (Islam N et al., 2015)

A Yale medical trial conducted by Dr. Brett A. King et al.(2014) found that Tofacitinib administered at a rate of 10mg per day completely reversed a case of alopecia universalis. The patient saw progress by the two month mark, with visible scalp and facial hair regrowth. A further three months therapy where the Tofacitinib dosage was increased to 15mg per day resulted in completely regrown scalp hair and visible eyebrows. By the end of the study at the eight month mark, the patient had completely recovered his scalp and bodily hair. The immensely promising results led Dr. Brett A. King to propose a clinical trial involving a tofacitinib topical solution.

JAK Inhibitors for Androgenic Alopecia (the most common form of hair loss)

some studies suggest that there might be untapped potential for JAK inhibitors

While alopecia areata and its more severe forms of alopecia universalis and alopecia totalis were in desperate need of a thoroughly tested and approved treatment, they constitute only a small percentage of all hair loss cases with androgenetic alopecia, also known as male pattern baldness, constituting the vast majority of cases.

When it comes to providing a solution to androgenetic alopecia, JAK inhibitors aren’t nearly as promising as their effects on alopecia areata.

Despite little known positive feedback when it comes to dealing with male pattern baldness, some studies suggest that there might be untapped potential for JAK inhibitors. In a study conducted on mice by Angela M. Christiano, one of the most ardent supporters of a JAK inhibitor solution for androgenetic alopecia, the inhibition of JAK-STAT signalling promoted hair growth. The study’s goal was to show the positive results of inhibition of JAK-STAT signalling for sufferers of alopecia areata. While results were satisfactory, the data also showed that the topical treatment of skin, both human as well as rodent, with small-molecule inhibitors of JAK-STAT resulted in the onset of anagen phase and subsequent hair growth cycle steps. During the study, Dr. Christiano and her team showed that JAK inhibition regulates the activation of key hair follicle populations while improving the inductivity of dermal papilla cells. (Christiano et al., 2015)

The promising results as well as Dr. Christiano’s research have led to Aclaris Therapeutics Inc. licensing a patent portfolio from Columbia University that aim to develop methods of using JAK inhibitors for the treatment of alopecia areata and adrogenetic alopecia as well as other dermatological conditions.

The portfolio is also made up of a U.S. patent which aims to develop methods of treating alopecia areata and androgentic alopecia as well as other hair loss disorders by administering ruxolitinib. Also included is a recently issued patent in Japan which is directed to pharmacetutical compositions made up of ruxolitinib, baricitinib as well as other JAK inhibitors with the goal of providing a treatment for androgenetic alopecia, alopecia areata and other hair loss disorders.

While research on JAK inhibitors as a solution for hair loss is still in its infancy, most studies suggest there is huge untapped potential. JAK inhibitors will most likely become one of the best ways to treat alopecia areata in the immediate future. Their role in the treatment of androgenetic alopecia is still being looked into, however, with numerous studies still being conducted and a topical solution being presently developed there is a good chance that they will play at least a role as an anti-inflammatory addition in hair loss treatment.

  1. Janus kinase inhibitors in dermatology: A systematic review 
    Shreberk-Hassidim R., Ramot Y., Zlotogorski A. (2016)  Journal of the American Academy of Dermatology, https://www.ncbi.nlm.nih.gov/pubmed/28169015
  2. Kennedy Crispin, M., Ko, J. M., Craiglow, B. G., Li, S., Shankar, G., Urban, J. R., … King, B. A. (2016). Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight, 1(15), e89776. https://www.ncbi.nlm.nih.gov/pubmed/27699252
  3. Kennedy Crispin, M., Ko, J. M., Craiglow, B. G., Li, S., Shankar, G., Urban, J. R., … King, B. A. (2016). Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight, 1(15), e89776. http://doi.org/10.1172/jci.insight.89776
  4. The autoimmune basis of alopecia areata: A comprehensive review
    Autoimmunity Reviews, Volume 14, Issue 2, Pages 81-89
  5. Naseeha Islam, Patrick S.C. Leung, Arthur C. Huntley, M. Eric Gershwin https://www.ncbi.nlm.nih.gov/pubmed/25315746
  6. Killing two birds with one stone: Oral tofacitinib reverses alopecia universalis in a patient with plaque psoriasis 
    Craiglow B.G., King B.A.  (2014)  Journal of Investigative Dermatology,  134  (12) , pp. 2988-2990. https://www.ncbi.nlm.nih.gov/pubmed/24940651
  7. Harel, S., Higgins, C. A., Cerise, J. E., Dai, Z., Chen, J. C., Clynes, R., & Christiano, A. M. (2015). Pharmacologic inhibition of JAK-STAT signaling promotes hair growth. Science Advances, 1(9), e1500973. http://doi.org/10.1126/sciadv.1500973 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4646834/