Rheumatoid Arthritis Drug Decreases Gut Leakiness, Study Says

Researchers have found that tofacitinib, an orally administered pan-Janus kinase (JAK) inhibitor approved by the US Food and Drug Administration to treat rheumatoid arthritis (RA) and ulcerative colitis, might also treat leaky gut, a digestive condition characterized by increased permeability in the gut’s epithelium. Their findings were published in Inflammatory Bowel Diseases.¹

Ulcerative colitis is a chronic inflammatory bowel disease (IBD) that causes inflammation and ulcers in the digestive tract.² It’s estimated that as many as 1.6 million Americans have ulcerative colitis or another IBD.³ Many patients with the condition have increased intestinal permeability, which exacerbates inflammation in the intestines.⁴

The investigators took samples of human intestinal epithelial cells and observed the effects tofacitinib had on them. They found that the JAK inhibitor improved function in the epithelial barrier, which is responsible for preventing bacteria and toxins from leaking through the intestinal wall.¹

“We found tofacitinib fixes the leakiness in the intestinal barrier,” explained Declan McCole, PhD, professor of biomedical sciences at the University of California, Riverside School of Medicine and lead author of the study. “Specifically, it fixes intestinal epithelial permeability defects caused by ‘interferon-gamma,’ an inflammatory cytokine involved in autoimmune diseases such as ulcerative colitis and rheumatoid arthritis.”⁵

Prior to this study, researchers were confident that tofacitinib helped with ulcerative colitis, but they weren’t sure how. “We now better understand where in the gut the drug is working, and how,” Dr McCole added.

Going forward, the researchers hope to identify specific patients who may benefit most from the drug as doing so would allow for more targeted treatments.

References

1. Sayoc-Becerra A, Krishnan M, Fan S, et al. The JAK-inhibitor tofacitinib rescues human intestinal epithelial cells and colonoids from cytokine-induced barrier dysfunction [published online November 21, 2019]. Inflamm Bowel Dis. 2019;pii:izz266. doi: 10.1093/ibd/izz266
2. Ulcerative colitis. Mayo Clinic. Updated December 24, 2019. Accessed January 3, 2020.
3. The facts about inflammatory bowel diseases. Crohn’s & Colitis Foundation of America. November 2014. Accessed January 3, 2020.
4. Mu Q, Kirby J, Reilly CM, Luo XM. Leaky gut as a danger signal for autoimmune diseases. Front Immunol. 2017;8:598.
5. Pittalwala I. Drug decreases gut leakiness associated with ulcerative colitis. University of California, Riverside website. December 4, 2019. Accessed January 3, 2020.