Treating sarcoidosis with JAK inhibitor shows promise in clinical trial

Every patient in a Yale clinical trial of a new treatment for the disfiguring disease sarcoidosis saw improvement to their skin-and more than half showed improvement in affected internal organs.

Sarcoidosis is a disease affecting four out of every 10,000 people in the United States. In sarcoidosis, abnormal collections of immune cells called granulomas may occur in the lungs, skin, heart, lymph nodes, eyes, and other organs, causing damage. Lesions involving the skin may be skin-colored or pink and often affect the face and may scar.

The late comedian Bernie Mac suffered from sarcoidosis and, indeed, Black people are more often affected by the disease than others. The only approved therapy for sarcoidosis is the steroid prednisone, which carries significant side effects.

For the new clinical trial, a Yale team led by Drs. William Damsky and Brett King treated 10 patients with tofacitinib, a Janus kinase (JAK) inhibitor normally used to treat rheumatoid arthritis and other autoimmune diseases.

The patients ranged in age from 53 to 63 and had lived with sarcoidosis for an average of 13 years. All of the patients had skin sarcoidosis; nine of the patients also had an internal organ that was being affected.

"Sarcoidosis can be a devastating disease and is often difficult to treat. We were excited to find that this treatment approach really appears to hold great promise," said Damsky, an assistant professor of dermatology and dermatopathology at Yale Medical School and first author of a new study about the clinical trial in the journal Nature Communications.

In the clinical trial, patients received tofacitinib for six months. All patients experienced significant improvement in their skin sarcoidosis-with six patients seeing a complete recovery.

Five of the nine patients with affected internal organs saw improvement in those organs, as well. Internal organ sarcoidosis was measured by using positron emission tomography (PET) scans; the five improving patients in the clinical trial experienced a reduction in internal organ disease of more than 50%.

Several patients reported significant improvement in their sinuses after treatment. Sarcoidosis can cause inflammation of the sinuses, leading to congestion, nose bleeds, and pain. Another patient, whose voice had been hoarse for more than a decade due to sarcoidosis in her larynx, had her voice return to normal with treatment.

The researchers said tofacitinib proved effective because it suppressed interferon-gamma, an immune system protein that is a key driver of sarcoidosis. "This work is important not only for its significant advancement of science and medicine but also because sarcoidosis disproportionately affects Black people," said King, associate professor of dermatology at Yale Medical School and co-corresponding author of the study.

"We need to advocate for medical care for all, not just the majority, and our work highlights what can be achieved in this area when we try," King said. In recent years, King and his collaborators have conducted pioneering research using JAK inhibitors to treat a variety of conditions, including alopecia areata, eczema, vitiligo, granuloma annulare, and erosive lichen planus.

Co-authors include Alice Wang, Daniel Kim, Bryan Young, Katelyn Singh, Michael Murphy, Joseph Daccache, Changwan Ryu, Meaghan McGeary, Ian Odell, Ramesh Fazzone-Chettiar, Darko Pucar, Robert Homer, Mridu Gulati, Edward Miller, Marcus Bosenberg, and Richard Flavell, all from Yale.

Additional co-authors are Abigale Clark of Kansas City University of Medicine and Biosciences and Ruveyda Ayasun of New York University Langone Medical Center.

The research was funded, in part, by Pfizer, The Dermatology Foundation, the Robert E. Leet and Clara Guthrie Patterson Trust, and the Ranjini and Ajay Poddar Fund for Dermatologic Diseases Research.

King is a consultant to and a speaker and clinical trial investigator for Pfizer, the maker of tofacitinib. Damsky is a consultant for Pfizer.