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JAK Inhibitors Research - a summary from Dr Susan Holmes

1st December 2016

There continues to be much media coverage about the research studies taking place in the USA into the use of JAK inhibitors as a treatment for alopecia areata. We asked dermatologist Dr Susan Holmes, who presented at our Big Weekend event earlier in the year, for a summary on the current research that is happening:

"Since the seminal paper from Angela Christiano`s group published in Nature Medicine in 2014, there has been considerable interest and excitement about the potential role of a group of drugs called JAK inhibitors in the treatment of alopecia areata. In the original paper, 3 patients with moderate to severe alopecia areata were treated with ruxolitinib tablets 20mg twice daily for 3-5 months and all developed complete or near complete hair regrowth. Now, the results of the first clinical trials of these drugs have been published in two papers in the journal JCI Insight. One paper documents the use of tofacitinib tablets in 66 patients with moderate to severe alopecia areata and the second paper describes the use of ruxolitinib tablets in 12 patients with moderate to severe alopecia areata. 

In the first study examining ruxolitinib, 12 patients (7 women and 5 men, average age = 43 years) with moderate to severe alopecia areata were given ruxolitinib tablets (20mg twice daily) for 3-6 months. Nine out of twelve patients had an excellent response to treatment, with at least 92% hair regrowth. No patients had any serious side effects. After treatment was stopped, 3 of 9 responders started shedding hair after 3 weeks and had marked loss by 12 weeks off the drug. However, hair loss did not reach pre-treatment levels.

In the second larger study, 66 patients (31 women and 35 men, average age = 37 years) with moderate to severe alopecia areata (including alopecia totalis and universalis) were given tofacitinib tablets 5mg twice daily for 3 months. The results were as follows:

- 36% of patients had no response

- 32% had an intermediate response (5-50% change in alopecia SALT (Severity of Alopecia Tool) score

- 32% had a more than 50% improvement in alopecia SALT score)

When further details were analysed, those with patchy disease (as opposed to universalis or totalis), those who had had alopecia for a shorter time and those with scalp inflammation on scalp skin biopsy were more likely to respond to the treatment. After the treatment was stopped, all 20 responders who were followed up, lost their hair by 8-9 weeks. No patients had serious side effects from the drugs.
The results of these trials are interesting but it is clear that more work needs to be done. Bigger and better trials are needed in order to confirm what proportion of individuals are likely to get a significant benefit from these drugs, ideally to the point where they no longer require wigs or significant camouflage, and who is most likely to do well with the treatment. 

We also need to know whether the benefits persist if the drug is continued for more than just a few months and whether the drug works in a wider range of people. Importantly, we need to confirm whether there are any serious long term side effects. As JAKIs are now being used in people with psoriasis and eczema, we may be able to get some information on drug safety from larger studies into other skin conditions. 

Both of these trials were open label studies –in other words, both the patients and their doctors knew that they were taking the drug. Neither trial included controls (patients who are given an inactive drug substitute known as a placebo). Ideal clinical trials are:

 - placebo controlled – half the participants are given a placebo

 - randomised – patients are randomly allocated to receive either drug or placebo

 - double-blinded – neither doctor nor patient know whether they are getting the study drug or      placebo. This is revealed at the end of the assessment period. 

Randomised double-blinded placebo-controlled trials are the best way of ensuring that the effects of a drug are assessed in an objective and unbiased way. As these sorts of studies are very expensive to run, it is essential that funding is made available to carry them out.

The scientific research which is currently being undertaken into alopecia areata is leading to a much better understanding of how the condition occurs and there are early trials investigating other possible new treatments for alopecia areata. In addition, there is much interest in whether topical JAK inhibitors (applied to the skin as a cream) will be useful in alopecia areata."

Thank you to Dr Holmes for providing this summary. We continue to follow the latest research taking place with great interest and hope that it will lead to better treatments for those with alopecia areata.  




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Alopecia UK is a registered charity number 1111304 and Scottish registered charity SCO44702
All content is © Alopecia UK 2017

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