Making it stick: New vitiligo research yields promise for lasting results

For patients facing a menacing and socially debilitating vitiligo diagnosis, a promising and potentially long-lasting treatment is within reach. John E. Harris, MD, PhD, associate professor of dermatology at the University of Massachusetts Medical Center, delivered that hopeful update during his Friday Plenary (P151) lecture Translational Research in Vitiligo: Launching a New Era of Targeted Treatments.”

John E. Harris, MD, PhD.

A common autoimmune disease of the skin, vitiligo is characterized by the appearance of white spots that result from the elimination of melanocytes by T cells. It affects between 2 and 3 million people in the U.S. and can occur at any age. However, most people experience symptoms before the age of 20. The condition is often associated with type 1 diabetes, Hashimoto thyroiditis, pernicious anemia, alopecia areata, and Addison’s disease.

Dr. Harris’ grandmother and great uncle had vitiligo, but that’s not what prompted him to study the condition. While initially studying diabetes, it was an encounter with a patient in the ICU who shifted his focus. The patient was simultaneously diagnosed with diabetes, thyroiditis, pernicious anemia, and vitiligo. It was an uncommon combination.

Condition still carries global stigma

“One of my patients told me that on the flight he took to my clinic, the woman next to him asked to change seats because of the spots on his arms. In south Asia, and in India, in particular, vitiligo was once confused with the infectious disease leprosy, which is endemic in the region,” Dr. Harris said. “Even today, India’s culture of arranged marriage still ostracizes those who have vitiligo; not only those with the disease but also their siblings can be eliminated as marriage prospects. And in the United Kingdom, a man who was originally from Pakistan reportedly asked for advice on how to arrange amputation of part of his arm, which showed signs of vitiligo. He said that his family would accept him with just one arm, but not with the condition.”

New studies offer insights

New research suggests that changes in a person’s immune system are at the root of the disease. While there are no FDA-approved medical treatments to reverse it, Dr. Harris’ research and the first large, randomized clinical trial by Incyte Corporation show promise for getting better treatments into the hands of patients in the near future.

“We determined that IFNg drives vitiligo progression through chemokines that promote T cell recruitment into the skin and hypothesized that targeting this pathway could be an effective treatment for patients,” Dr. Harris said. “Early proof-of-concept studies demonstrated that JAK inhibitors, which block IFNg signaling, reversed vitiligo in a small number of vitiligo patients. Now a large, randomized, multicenter clinical trial has confirmed these observations.”

New and emerging treatments provide hope

Current treatments include phototherapy as well as topical immunomodulators such as steroids and calcineurin inhibitors. Emerging treatments include JAK inhibitors, such as tofacitinib and ruxolitinib. These drugs, which can be used orally or topically, target signaling by the cytokine interferon gamma. However, the problem with the current treatments is that the benefits don’t last, Dr. Harris said. Once patients stop using these treatments, the condition may relapse almost immediately.

Researchers now know that autoreactive resident memory T cells from within the vitiligo lesions themselves are responsible for the relapse, he said. Similarly, Dr. Harris’ research revealed that cytokine interleukin 15 (IL-15) is required for the survival and maintenance of these cells in those lesions. In mouse models and clinical trials, targeting IL-15 reverses vitiligo for a longer period of time.

The future of vitiligo treatment

Today, Dr. Harris credits his research success to “seamless integration of clinical, translational, and basic research.” And he believes a more permanent remedy is just a few years away.

“If all goes well, I expect the first FDA-approved medication to reverse vitiligo should be approved within the next three to five years,” he said. “For the ‘next generation’ treatments that will hopefully provide durable results, we will need to continue our research with an eye toward clinical trials on a rapid timeline. If we can do that and the results are good, then we are optimistic that they will be available to patients within the next five to 10 years. Of course, these are a lot of ‘ifs,’ but we are motivated to help these patients by creating safer and more effective treatments for them. We are also working to find a permanent cure!”