Researchers report early success with using an existing rheumatoid arthritis (RA) drug to treat systemic sclerosis, a rare but potentially devastating autoimmune condition.
The disease, a subset of scleroderma, hardens the skin and affects internal organs, but no approved treatment for it exists.
So, the research team from the University of Michigan and University of Pittsburgh decided to study whether the RA drug tofacitinib (Xeljanz) might work in early stages of the disease. To do that, they worked with 15 patients who had early systemic sclerosis.
While 10 of the patients received 5 milligrams of tofacitinib twice a day, the other five received a placebo for the 24 weeks of the study.
The researchers found that the treated patients had improved Rodnan skin scores (mRSS), which measures skin thickening, and improvements in other measures. Patients assigned to the placebo were given the medication after the trial ended, and they showed improvement over the next 24 weeks.
“We are delighted to find that the drug is safe to use and can possibly be repurposed for systemic sclerosis treatment,” said study author Dr. Dinesh Khanna, director of the Michigan Medicine Scleroderma Program. “But what made this study innovative was the use of single-cell technology.”
Patients had their skin biopsied at the start of the trial and again six weeks later. The researchers used a newer technology, called single-cell RNA sequencing, to watch how tofacitinib worked on the skin cells.
“We wanted to understand first, if there was any clinical benefit of tofacitinib to patients, but we were also asking, what are the differences in the cells of healthy skin versus systemic sclerosis cells… how does the drug work?” Khanna said in a Michigan Medicine news release.
According to study co-author Dr. Johann Gudjonsson, a professor of dermatology at the University of Michigan, “This work highlights the ability of single-cell RNA sequencing to determine how disease states are maintained and how various cell populations in the skin — both fibroblasts, skin cells and immune cells — communicate, providing unparallelled power to address disease mechanisms, and how drugs like tofacitinib work in a disease where they have not previously been used."
While the study showed tofacitinib inhibits the cells that help form connective tissue and skin cells (fibroblasts and keratinocytes), it also found it had minimal effect on T-cells, which are white blood cells that are essential for the immune system.
Systemic sclerosis affects 100,000 people in the United States. Most are women.
“From this combined effort between Michigan Medicine and University of Pittsburgh, we know that the drug is safe, and we know that the technology (RNA sequencing) is feasible. Now we can start to utilize the technology and find out what type of therapies we can mix and match that will add benefit to patients,” Khanna said.
Pfizer Inc. funded the study, but had no role in collecting, analyzing and interpreting the data.
The findings were published online recently in the journal JCI Insight.
The U.S. National Library of Medicine has more on systemic scleroderma.
SOURCE: Michigan Medicine -- University of Michigan, news release, Oct. 6, 2022