A day after the new rheumatoid arthritis drug Xeljanz was reported to slow the progression of RA, a study published in the Journal of Clinical Investigation says scientists have identified a potential new way to attack the systemic inflammatory disorder.

Researchers at the Hospital for Special Surgery (HSS) in New York City reported that a protein, IRHOM2, could be targeted to treat RA in an effective and less toxic way compared to the current option, tumor necrosis factor-alpha blockers (TNF-blockers). TNF-blockers, such as Enbrel, Remicade, and Humira, have been the primary treatments for rheumatoid arthritis for over a decade.

Despite their effectiveness in slowing the progress of RA, and keeping joint damage at bay, these complex and expensive drugs also come with potentially dangerous side effects. TNF-blockers have been linked to an increased risk of cancer and serious infections, and they are also unsuccessful with some rheumatoid arthritis patients.

Researchers hope a new class of drugs, targeting IRHOM2 rather than blocking tumor necrosis factor-alpha (TACE), could help lower the price of treatment, reduce side effects, and increase the success rate of RA treatment.

"This study is an elegant example of the capacity of basic-science cell biologists to work with translational rheumatologists to address a clinically relevant question at a basic level," said study author Jane Salmon, M.D., Collette Kean Research Chair and co-director, Mary Kirkland Center for Lupus Research at HSS, in a press release. "We have identified a clinically relevant target that can be applied to patients in the near term."

After determining that the IRHOM2 protein regulates an enzyme on immune cells — TNF-alpha converting enzyme (TACE) — that can be responsible for RA, researchers looked at whether blocking IRHOM2 would have an effect on rheumatoid arthritis symptoms. Using genetically engineered mice that were deficient in the protein, they found that blocking IRHOM2 kept the mice from developing inflammatory arthritis.

"[W]e found they were protected, and they were protected as well as mice that didn't have any TNF," said Carl Blobel, M.D., Ph.D., program director of the Arthritis and Tissue Degeneration Program at HSS. "Because TNF is the driver of rheumatoid arthritis in human disease, as evidenced by how well anti-TNF drugs work, we feel that this provides a completely new angle on blocking TNF release." IRHOM2 seems to provide a novel way for the researchers to do this, he added.

The next step is to identify antibodies or compounds that can be used to block the function of IRHOM2 and are safe in patients. The HSS investigators are working on this now.