Pilot Study to Evaluate the Efficacy of Ruxolitinib in Alopecia Areata

Overview

Alopecia areata (AA) is a common disease of the immune system, known as an "autoimmune" disease. In the disease, the immune system mistakenly destroys the hair follicle, causing hair to fall out. Despite many people having this disease, research into its cause and into new, better ways to treat AA has lagged far behind other similar diseases of the immune system. Currently, there are no Federal Drug Administration approved drugs for AA. Ruxolitinib (made by Incyte) is an intervention known to effectively treat a disease of the bone marrow, known as myelofibrosis. It is also being studied in the treatment of rheumatoid arthritis, another "autoimmune" disease, by fighting inflammation. There are some genetic and chemical similarities between those with myelofibrosis, active rheumatoid arthritis and AA, suggesting that treatment with ruxolitinib may be effective in AA. In mice specially designed for testing drugs for the treatment of human alopecia areata, this medication worked to prevent the disease AA from starting in mice that would have otherwise developed the disease. To test Ruxolitinib, we are going to treat 12 patients with moderate to severe AA for a minimum of 3 months up to 6 months. This is an "open-label" study, meaning that there will not be a placebo group; all patients enrolled in the study will receive the active medication. The effectiveness of the medication will be measured by changes in hair re-growth as determined by physical exam and photography, as well as by patient and physician scoring. Patients will be followed for another 3 months off of the drug to see if the effects of treatment last and if there is delayed response. The safety of the medication, ruxolitinib, in patients with alopecia areata will also be evaluated. Blood work will be collected before medication is started, during the treatment period, and after ruxolitinib is stopped, in order to monitor for adverse effects of the medication. Small scalp biopsies and peripheral blood will be taken at the beginning of the study before treatment and also after 12 and possibly 24 weeks. Optional biopsies may also be taken at additional time points based on clinical considerations. The chemical analysis of these skin samples and blood will help us to understand how the disease happens, how the treatment works, and may even guide us to better treatments in the future.

Alopecia areata (AA) is a common autoimmune disease resulting from immune destruction of the hair follicle and subsequent hair loss. Despite its high prevalence, research into the pathogenesis and the development of innovative therapies in AA has lagged far behind other autoimmune diseases. Currently, there are no FDA approved drugs for AA. Ruxolitinib (Incyte) is an intervention known to effectively treat myelofibrosis and also rheumatoid arthritis by modulating the inflammatory response of the interferon response pathway by inhibition of Jak1/Jak2. Rheumatoid arthritis shares several susceptibility genes in common with AA. All three diseases share the central role of the interferon-gamma response pathway, which is the rationale for selecting Ruxolitinib for evaluation in this clinical trial. Both systemic and topical Ruxolitinib have been shown to prevent the onset of AA in the C3H-HeJ animal model of AA, demonstrating preclinical proof-of-concept data in AA. To test the safety and efficacy of Ruxolitinib in patients with moderate to severe AA, we propose this open-label, single arm pilot study with a total of 12 patients, treated for a minimum of 3 months up to 6 months. Efficacy will be measured by changes in hair re-growth as determined by physical exam and photography, as well as by patient and physician global evaluation scores. Patients will be followed for another 3 months to evaluate durability of response following the treatment phase. Punch biopsies and peripheral blood will be obtained at baseline prior to treatment and then after 12 and possibly 24 weeks for immune monitoring and for molecular studies.