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JAK Inhibitors Prove Effective in Trials on Alopecia Areata

October 25th, 2016

Two new studies researching a class of drugs called JAK inhibitors have shown that oral treatment results in significant hair regrowth in patients with alopecia areata, an autoimmune condition that causes non-scarring patches of localized hair loss. Currently there is no cure for alopecia areata, so the possibility of a safe, effective medication is welcome news for thousands of affected patients.

Background

Last year we wrote about how the two new FDA-approved drugs tofacitinib and ruxolitinib act as inhibitors of the family of enzymes called Janus kinase (JAK).[1] By inhibiting the JAK enzymes, the drugs disrupt intracellular communication to white blood cells, called “T lymphocytes,” and are thus useful in treating alopecia areata. The JAK inhibitors prevented the onset of the disease and reversed the condition, enabling hair to regrow in areas previously devoid of hair.

The 2015 study we referenced – led by renowned alopecia areata researcher Dr. Angela Christiano – showed that topical application of tofacitinib and ruxolitinib in mice resulted in the rapid transition of hair follicles from the telogen (resting) phase of the hair cycle to the anagen (growth) phase. The same study found that tofacitinib encouraged hair follicle development in clumped human dermal papilla (DP) cells, stem cells that are critical in the development of hair follicles. [1]

The Studies

The two new studies were published in September 2016 in the journal JCI Insight, a peer-reviewed journal dedicated to biomedical research.

Tofacitinib

The study of oral tofacitinib – by Crispin, Ko, et al – was a 2-center, open-label, single-arm trial; the first to systematically examine the efficacy of JAK inhibitors as a treatment for alopecia areata.[2] In addition to studying alopecia areata (AA) patients with greater than 50% scalp hair loss, they tested the drug on patients with alopecia totalis (AT), which is the complete loss of scalp hair; alopecia universalis (AU), the loss of scalp and body hair; and ophiasis pattern alopecia areata, hair loss localized to the temporal and occipital scalp. After three months on 5mg tofacitinib citrate, 32% showed up to 50% improvement, and 32% showed greater than 50% improvement. When broken down by subtype of the condition, those with AA improved by 70% on average, those with ophiasis improved by 68%, AT by 11.8%, and AU by 10.5%. They found that following cessation of the treatment, all patients experienced a recurrence of hair loss after an average of 8.5 weeks. Additional trials are necessary to determine the optimal dosage regimen for providing the most long-lasting response.

Ruxolitinib

The study of ruxolitinib – by Mackay-Wiggan, Jabbari, et al – was an open-label clinical trial of 12 patients with moderate to severe alopecia areata. [3] The pilot study tested the use of 20mg oral ruxolitinib twice a day for three to six months; this was followed by three months of monitoring the patients without treatment. Despite the small sample size, the results were striking in that 75% of patients showed a strong response to the medication, with hair regrowth over 50%. After treatment, those who responded to the treatment exhibited a 92% reduction in hair loss. Seven of the nine responders achieved greater than 95% hair regrowth. After stopping treatment hair loss resumed; however, it did not reach the level of hair loss that was present before treatment. This proof-of-concept pilot study showed that ruxolitinib is a safe and effective in reversing the balding effects of alopecia areata.

Conclusion

After showing promise in previous research, scientists have now shown that JAK inhibitors have strong potential to cause substantial hair regrowth in people with alopecia areata; a condition that causes hair loss that can be socially awkward at best and cosmetically disfiguring in severe cases. More studies need to go forward in order to determine which of the two drugs – tofacitinib or ruxolitinib – will be the most effective treatment, and what the proper dosage is for long-term treatment. However, we are hopeful that a medication will be developed for broad use in treating alopecia areata patients.

The other major point of interest following the publication of the series of studies is the potential for JAK inhibitors to treat androgenetic alopecia, or common genetic hair loss. One area that is being discussed is the potential for JAK inhibitors, perhaps in the form of a topical treatment, to stimulate the transition of hair follicles from the resting phase to the growth phase of the hair cycle. Christiano’s research is examining the effects of JAK inhibitors on cultured dermal papilla (DP) spheres. If JAK inhibitors can be used to stimulate DP spheres to grow into mature hair follicles, it may enable hair multiplication techniques to become a viable treatment for common baldness.

References:
  1. Harel S, Higgins CA, Cerise JE, Dai Z, Chen JC, Clynes R, Christiano AM. Pharmacologic inhibition of JAK-STAT signaling promotes hair growth. Sci Adv. 2015 Oct; 1(9): e1500973. []
  2. Crispin MK, Ko J, Craiglow BG, Li S, Shankar G, Urban JR, Chen JC, Cerise JE, Jabbari A, Winge MG, Marinkovich MP, Christiano AM, Oro AE, King BA. Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight. 2016;1(15):e89776. doi:10.1172/jci.insight.89776. []
  3. Mackay-Wiggan J, Jabbari A, Nguyen N, Cerise J, Clark C, Ulerio G, Furniss M, Vaughan R, Christiano AM, Clynes R. Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata. JCI Insight. 2016;1(15):e89790. doi:10.1172/jci.insight.89790. []



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