Tuesday, June 24, 2014

New treament for Alopecia universalis

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Alopecia universalis occurs in approximately one in every 200,000 people. It is thought to be an auto immune disorder and can affect anyone at any age, long considered untreatable.

An arthritis drug Tofacitinib citrate (trade names Xeljanz and Jakvinus, formerly tasocitinib or CP-690550 & developed at Pfizer) was used to treat the 25-year-old man Kyle Rhodes from Killingworth who had lost most of his hair of the scalp, face and body by his 18th birthday, after getting alopecia universalis – a disease there is currently no long-term treatment or cure for. The only hair on his body was within the psoriasis plaques on his head.

Kyle Rhodes visited Assistant Professor of Dermatology at Yale University School of Medicine, Dr. Brett King late last summer, seeking help for a severe case of plaque psoriasis & associated Alopecia universalis. The man had not grown hair for seven years. However, after being treated with Tofacitinib just three months, he had regrown a head of hair, eyebrows, eyelashes, some facial hair and armpit hair. This is a huge step forward in the treatment of patients with this condition.

The patient's head a) before treatment with Tofacitinib, b) two months into treatment, c) five months into treatment, and d) eight months into treatment. Yale University

King believed it might be possible to address both diseases simultaneously using an existing FDA-approved drug for rheumatoid arthritis called Tofacitinib citrate. The drug had been used successfully for treating psoriasis in humans. It had also reversed alopecia areata, a less extreme form of alopecia, in mice as studied (but not published) by Columbia University scientist Angela Christiano.


After two months on Tofacitinib at 10 mg daily, the patient’s psoriasis showed some improvement, and the man had grown scalp and facial hair — the first hair he’d grown there in seven years. After three more months of therapy at 15 mg daily, the patient had completely regrown scalp hair and also had clearly visible eyebrows, eyelashes, and facial hair, as well as armpit and other hair. By eight months there was full regrowth of hair, The patient has reported feeling no side effects, and lab test showed no abnormalities, either.

It is believed that Tofacitinib appears to spur hair regrowth in a patient with alopecia universalis by turning off the immune system attack on hair follicles that is prompted by the disease.

King has submitted a proposal for a clinical trial involving a cream form of tofacitinib as a treatment for alopecia areata. A topical formulation has yet to be developed and will be difficult to develop due to the large size of the molecule involved and consequent difficulty in penetrating the scalp skin.

The paper is titled “Killing Two Birds with One Stone: Oral Tofacitinib reverses Alopecia Universalis in a Patient with Plaque Psoriasis.”

Mechanism of action
Tofacitinib is an inhibitor of the enzyme janus kinase 3 (JAK3), & it interferes with the JAK-STAT signaling pathway, which transmits extracellular information into the cell nucleus, influencing DNA transcription.

Recently it has been shown in a murine model of established arthritis that Tofacitinib rapidly improved disease by inhibiting the production of inflammatory mediators and suppressing STAT1-dependent genes in joint tissue. Tofacitinib may exert therapeutic benefit via pathways that are not exclusive to inhibition of JAK3. In November 2012, the U.S. FDA approved Tofacitinib for treatment of rheumatoid arthritis. Once on the market, rheumatologists complained that the $2,055 a month wholesale price was too expensive.

Possible side effects:
The most important side effects in Phase II studies were increased blood cholesterol levels and neutropenia. Phase III trials testing the drug in rheumatoid arthritis started in 2007 and are scheduled to run until January 2015. In April 2011, four patients died after beginning clinical trials with tofacitinib. By April 2011, three phase III trials for RA had reported positive results. In November 2012, the U.S. FDA approved Tofacitinib "to treat adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to, or who are intolerant of, Methotrexate." A boxed warning that goes along with this approval warns patients that they are at higher risk of opportunistic infections, tuberculosis, cancers and lymphoma.

* This case report was publishes in Journal of Investigative Dermatology on 18th June 2014 by Dr. Brett King & Brittany G Craiglow at Yale University School of Medicine: online available at: http://www.nature.com/jid/journal/vaop/naam/pdf/jid2014260a.pdf

The paper is titled “Killing Two Birds with One Stone: Oral Tofacitinib Reverses Alopecia Universalis in a Patient with Plaque Psoriasis.”

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