Rinvoq Found Safe, Effective for Ulcerative Colitis in Ongoing Phase 3 Trial

Rinvoq Found Safe, Effective for Ulcerative Colitis in Ongoing Phase 3 Trial

Rinvoq (upadacitinib), AbbVie‘s investigational anti-inflammatory medicine, was found to be safe and effective in treating adults with moderate-to-severe ulcerative colitis (UC).

The medication met all major endpoints in an ongoing Phase 3 trial (NCT02819635), called U-ACHIEVE, with 26% of patients achieving complete clinical remission after treatment, compared to 5% of those in the placebo group.

“Despite the availability of multiple treatment options with varying mechanisms of action, many patients still do not achieve disease control,” Michael Severino, MD, vice chairman and president of AbbVie, said in a press release.

“We are encouraged by these results showing upadacitinib’s potential to improve clinical, endoscopic and histologic outcomes in patients with ulcerative colitis,” he said.

Rinvoq is an oral anti-inflammatory medication that reduces autoimmune and other pro-inflammatory responses by blocking a family of signaling molecules called JAK proteins. The therapy has been approved as a treatment for rheumatoid arthritis and is now being investigated for UC and Crohn’s disease.

The U-ACHIEVE trial, which is still recruiting participants, compares Rinvoq’s safety and efficacy to placebo in participants, 16 to 75 years old, who have experienced UC for at least 90 days before entering the study.

The proportion of patients achieving clinical remission by week eight is the trial’s main goal, or primary endpoint.

Secondary endpoints include: clinical response, specifically a decrease in Adapted Mayo score, which assesses the severity of UC, of at least two points and 30% or more from baseline (start of the study); endoscopic improvement and histologic-endoscopic mucosal improvement — a reduction in inflammation of the intestine’s mucus membrane, measured both by endoscopy and a tissue sample.

The trial met its primary endpoint, as more patients (26%) treated with Rinvoq (45 mg, once daily) achieved clinical remission at week eight compared to the placebo (5%).

Secondary endpoints were also met, as more Rinvoq-treated participants (73%) achieved clinical response at week eight compared to their placebo-treated counterparts (27%). Furthermore, 36% of patients in the treatment group saw endoscopic improvement at week eight, compared to 7% of those taking placebo, and 30% of the treated patients had histologic-endoscopic mucosal improvement compared to 7% in the placebo group.

Rinvoq’s safety was consistent with previous findings, with no new safety risks identified. The most frequently-reported adverse side effects were acne, increased blood creatine phosphokinase (a marker of inflammation), and nasopharyngitis (a cold).

The instances of elevated creatine phosphokinase were considered non-serious and none caused participants to leave the study early. Patients in whom this occurred tended to be asymptomatic. Investigators observed no cases of rhabdomyolysis — in which dying muscle fibers release their contents into the bloodstream — which can lead to serious complications such as kidney failure.

Serious adverse side effects occurred in 2.5% of individuals in the Rinvoq group, compared with 5.8% in the placebo group. Serious infections were reported in 1.6% of patients in the Rinvoq group and in 1.3% of the placebo group. No deaths, ruptured bowels, cancer, or major cardiovascular or blood clotting events were reported.

AbbVie plans to present full trial results at an upcoming medical meeting and submit them for publication in a peer-reviewed journal.

This trial is the first in a series of studies assessing Rinvoq’s efficacy, safety, and tolerability in more than 1,300 patients with moderately to severely active UC. The other two trials are either active but not enrolling (NCT03653026, U-Accomplish), or enrolling by invitation only (NCT03006068).

“Ulcerative colitis is a complex disease to manage, and many patients do not achieve relief from symptoms,” said Silvio Danese, MD, lead study investigator. “I am excited about these positive results showing the potential of upadacitinib to alleviate symptoms and control mucosal inflammation in patients with moderate to severe ulcerative colitis.”