A research team at Yale School of Medicine successfully treated a person with disfiguring sarcoidosis with Xeljanz (tofacitinib) — an existing approved treatment against rheumatoid arthritis — resulting in a near-complete disappearance of skin lesions.
The findings were published in the New England Journal of Medicine in an article titled “Tofacitinib Treatment and Molecular Analysis of Cutaneous Sarcoidosis.”
Sarcoidosis often occurs between ages 20-40, and is most commonly found in women. There is no cure, but while some patients recover without treatment, others need some form of therapy to reduce symptoms and maintain the function of affected organs.
Anti-inflammatory medications such as prednisone (a corticosteroid) or methotrexate are sometimes prescribed to manage sarcoidosis-related tissue inflammation. However, these treatments are often ineffective, and may cause serious side effects, such as increased infection susceptibility.
Previous evidence suggested that the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling plays a role in the development of sarcoidosis. The JAK-STAT pathway is known to be involved in several cellular processes, including immunity, cell division, and cell death.
On that basis, researchers tested whether Xeljanz — an inhibitor of the JAK-STAT pathway used to treat rheumatoid arthritis and other skin diseases, and marketed by Pfizer — could have a therapeutic effect on sarcoidosis patients.
A 48-year-old female patient with cutaneous sarcoidosis, who had not responded to conventional therapies and had not used glucocorticoids, received oral Xeljanz (5 mg) twice a day for several months.
The team assessed the levels of RNA and proteins in skin-lesion samples before and during therapy, and further compared the observations with samples from other patients with cutaneous sarcoidosis.
Researchers found that skin lesions nearly disappeared with Xeljanz treatment, and observed reduced activity of the JAK-STAT pathway. The patient did not experience any adverse effects from the treatment, and did not develop lung symptoms.
“Before treatment, we were able to show that the Jak-STAT pathway is activated,” Brett King, MD, PhD, senior author of the study, a consultant and clinical trials investigator for Pfizer, said in a Yale university news release written by Ziba Kashef. “During treatment, not only does her skin disease go away, but there is no activation of the pathway.”
According to the study’s co-author, Nkiruka Emeagwali, MD, PhD, the findings are an important step toward better understanding sarcoidosis, an otherwise little-known disease.
“We plan to evaluate the activation of the Jak-STAT pathway in the lung fluid and blood of over 200 patients with pulmonary and multiorgan sarcoidosis,“ Emeagwali said.
King added that the team is further testing the results with Xeljanz in a clinical trial (NCT03793439), which, if confirmed, could represent a breakthrough for sarcoidosis patients.
“A frequently awful disease, which to date has no reliably effective therapy, may now be targeted with Jak inhibitors,” King said. “We have a relatively safe medicine that works.”