UChicago Medicine builds on years of experience with first oral IBD treatment

A growing body of real-world evidence continues to show that upadacitinib, the first oral medication approved by the FDA to treat Crohn’s disease and the second drug in its class for ulcerative colitis, is not only safe but fast acting and effective. This makes it a novel and significant new option for patients with moderate to severe Crohn’s disease and ulcerative colitis.

In a new study evaluating the long-term safety of upadacitinib (marketed as Rinvoq) during six clinical trials, researchers found that rates of serious complications like blood clots in the legs, heart attacks, and cancer remained low throughout treatment.

“Ahead of its approval, I thought that this drug would be a game changer because it brings a new mechanism as well as a new, non-biological delivery system to patients with Crohn's disease and ulcerative colitis,” said David T. Rubin, MD, Director of the Inflammatory Bowel Disease Center at the University of Chicago Medicine. “These new data about its safety are reassuring, so that we can use it properly in more patients.”

Rubin is the senior author of the new study, which published in Clinical Gastroenterology and Hepatology.

A new, more effective way to do the job

Other FDA-approved drugs for IBD are so-called “biologic” treatments that use proteins like monoclonal antibodies to target other immune proteins that drive inflammation in many diseases. They are administered by injections or regular infusions, which can make them costly and inconvenient for many patients.

These biologic drugs also face another challenge in treating Crohn’s and ulcerative colitis: when the lining of the intestine is inflamed during a flare-up of the disease, it becomes more porous, letting these proteins leak through the bowel wall and therefore limiting their efficacy as an anti-inflammatory therapy.

Rinvoq is one of a new generation of drugs that are small molecules — small enough to be delivered effectively in a once-daily pill, allowing the treatment to be absorbed directly through the lining of the small intestine and avoid the leakage issue associated with biologic therapies.

Rinvoq is a Janus kinase (JAK) inhibitor, meaning it works by blocking an enzyme on the walls of cells. In this case, Rinvoq blocks one of four kinases (JAK-1) that shuts down three different inflammatory pathways, making it a potent and effective way to control inflammation.

“This is a novel treatment strategy that is not just a different mechanism of action, but, because of its delivery system, potentially a much more effective way to get the drug into people to do the job,” Rubin said.

In other studies, most patients began to improve after just three days of treatment; 21% reported feeling better after just one dose.

Real-world experience

The new paper is an analysis of clinical trials conducted by AbbVie, the manufacturer of Rinvoq. The drug was first approved by the FDA to treat rheumatoid arthritis in 2019, and later for ulcerative colitis (2022) and Crohn’s disease (2023).

Rubin and his colleagues at the IBD Center have spent years evaluating the real-world experience of patients taking Rinvoq and other new therapies for IBD. They were the first researchers in the world to publish about their experience treating Crohn’s and ulcerative colitis with Rinvoq in the real world in 2023, and this year, they were the first to publish data showing that patients responded well when higher doses of Rinvoq were reintroduced after they stopped responding to lower maintenance doses.

“We have such a large set of patients and now we're on the cutting edge of using these therapies. We're working at the regulatory level, we're working with clinical trials, and we're working with patients in the clinic in the real world,” Rubin said.

“We are proud to have one of the fastest and most prolific real world data centers in IBD at UChicago, thanks to our large, amazing patient population and our collaborative work across disciplines. The real-world experience is a critical part of understanding how to treat people with these immune conditions more effectively and safely.”

Disclosure: David T. Rubin is a paid consultant of AbbVie, Bristol Myers Squibb, Johnson & Johnson, and Pfizer, the makers of therapies for IBD including Rinvoq, Xeljanz, and Velsipity.