CHARLOTTE, N.C.—A higher dose of upadacitinib is more effective than a lower dose for maintenance therapy in patients with ulcerative colitis, according to the results of a new study presented at the 2022 annual meeting of the American College of Gastroenterology. The agent also was shown to be effective in the investigational setting as maintenance therapy for Crohn’s disease in another study presented at the meeting.

Upadacitinib (Rinvoq, AbbVie) has proven to be effective as an induction and maintenance therapy in patients with UC, but it has been unclear whether a 30-mg dose had advantages over a 15-mg dose for maintenance. To investigate which regimen is superior, researchers at multiple institutions evaluated the effects of low- and high-dose regimens in patients who responded to the agent as an induction therapy.

The team analyzed patients who were randomly assigned to receive 15 mg (n=149) or 30 mg (n=148) of upadacitinib or placebo (n=154), defining clinical response as a decrease of at least 2 points in the Adapted Mayo Score and a decrease of more than 30% from baseline in that score, with a minimum drop in the rectal bleeding score of 1 or more.

“The outcomes we were interested in were the percentage of patients with mild, moderate and severe disease at week 52 as defined by Partial Mayo scores of less than 5, 5 to 7 and greater than 7, respectively,” said lead investigator Brian Feagan, MD, a professor of medicine at the Schulich School of Medicine and Dentistry at Western University, in London, Ontario, who presented the results of the U-ACHIEVE phase 3 maintenance trial (oral presentation 1/ abstract S712). The investigators also looked at the proportion of patients in clinical remission at week 52 as defined by a rectal bleeding score of 0 or a stool frequency score of less than 1.

At baseline, more than 90% overall had mild disease, and no patients had severe disease, given that all responded to the induction phase. By week 52, nearly 20% more patients in the 30-mg group had less severe disease than those in the 15-mg group, with severe disease seen in approximately 10% of the 30-mg group and approximately 19% of the 15-mg group. The placebo group began to lose remission as early as four weeks into the trial.

“The two active therapy groups over time had an approximately 10% difference in remission rates by Partial Adapted Mayo Score, favoring the higher dose, with separation between the two at approximately 10 weeks,” Dr. Feagan said.

Regarding adverse events, Dr. Feagan told Gastroenterology & Endoscopy News that “there was not a specific comparison because of the low number of events,” but he noted that the full study results will be published later this year.

Safety Results Needed

There was no information about safety presented in the abstract, but Samir Shah, MD, a clinical professor of medicine at the Warren Alpert Medical School of Brown University, in Providence, R.I., said it would be of great interest to patients and physicians whether there were any safety differences between the two doses of upadacitinib.

“Assuming no safety differences, this would influence me to choose the higher dose of 30 mg for a better chance of maintaining remission over time,” Dr. Shah said, noting that these data are consistent with those on another Janus kinase (JAK) inhibitor, tofacitinib (Xeljanz, Pfizer), where the higher dose of 10 mg twice daily was superior to the lower dose of 5 mg twice daily for maintenance of remission.

Similar Results for CD

In a separate late-breaking abstract presented by Edward V. Loftus Jr., MD, a professor of medicine at Mayo Clinic in Rochester, Minn., upadacitinib was effective as a maintenance therapy in patients with moderate to severe Crohn’s disease who had responded to the JAK inhibitor in an induction trial (late-breaking abstract 44).

In the U-ENDURE maintenance trial of 502 patients, 165 were assigned to placebo, 169 to 15 mg of upadacitinib and 168 to 30 mg of upadacitinib. The primary end points were clinical and endoscopic remission.

The baseline characteristics were similar between the three groups, with 75% of patients having failed prior biologic treatment, “and a significant number who had failed three or more. The vast majority of the biologic failures had failed an anti-TNF,” Dr. Loftus said.

At the conclusion of the 52-week trial, significantly more patients in the upadacitinib groups had achieved clinical remission: 37% of those on 15 mg and 47% of those on 30 mg compared with 15% of those in the control arm (P<0.0001). Patients in the therapeutic arms also achieved greater rates of endoscopic response: 27% in the 15-mg group and 40% in the 30-mg group compared with 7% in the placebo group.

In terms of safety, serious adverse events occurred at slightly higher rates in the placebo group than in either upadacitinib group. “Looking at adverse events that occurred in more than 5% of the patients, the top three were nasopharyngitis, worsening of Crohn’s disease and upper respiratory tract infections,” Dr. Loftus said.

Positive Results In Very Sick Patients

Bincy Abraham, MD, MS, a professor of clinical medicine at Houston Methodist Academic Institute, noted that although there are two JAK inhibitors approved for UC, none have been approved yet for Crohn’s disease. She found the data impressive on a number of fronts.

“First, 75% of these patients had failed other biologics, so this was a sick group of people. Despite that, 40% of those on the higher dosage achieved endoscopic remission and almost half, 48%, achieved clinical remission,” Dr. Abraham said.

In addition, the adverse events were comparable between the placebo the active medication groups, she noted.

If the agent is approved in this setting, she said, “this would be our first oral small molecule for the treatment of Crohn’s disease.”

—Monica J. Smith

Drs. Abraham and Feagan reported financial relationships with AbbVie. Dr. Shah reported no relevant financial disclosures.