Extended Induction Upadacitinib Safe, Effective for Ulcerative Colitis

Edward V. Loftus, Jr, MD, FACG

Extended induction therapy with once-daily upadacitinib (Rinvoq) resulted in a clinically meaningful response in more than half of patients with moderately to severely active ulcerative colitis (UC) who did not respond to an initial 8-week induction period with the JAK inhibitor, according to findings from an open-label extension of the pivotal U-ACHIEVE and U-ACCOMPLISH trials presented at the American College of Gastroenterology (ACG) 2022 Annual Scientific Meeting in Charlotte, NC.

There was a 58.4% clinical response rate at week 16 with the extended 45-mg daily upadacitinib treatment (73 of 125). After responding to the extended therapy, patients were switched to a daily maintenance dose of upadacitinib at 15 mg (n = 34) or 30 mg (n = 39), with a dose dependent response seen at 52 weeks. In the 30 mg arm, 78.1% of patients continued to have a clinical response with upadacitinib. In the 15 mg arm, 49.1% had a clinical response at week 52.

"This shows that 16 weeks of extended induction treatment with upadacitinib 45 mg led to achievement of clinical response in a clinically meaningful proportion of patients who do not respond to 8 weeks of induction therapy," lead author Edward V. Loftus, Jr, MD, FACG, Professor of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, said during a presentation of the results. "The benefit of maintenance therapy was demonstrated with both upadacitinib 15 mg and 30 mg; however, the 30 mg dose provided a numerically greater benefit than the 15 mg dose across all clinical, endoscopic, and histologic end points."

In March 2022, the FDA approved upadacitinib as a treatment for patients with moderately to severely active UC who had an inadequate response or intolerance to TNF blockers. This approval, which added to several other for the medication, was based on findings from the U-ACHIEVE and U-ACCOMPLISH trials, which enrolled 664 patients to receive 45-mg once daily upadacitinib for an 8-week induction period.

Baseline characteristics in the 73 patients who were randomized to maintenance therapy varied between doses. For the 15 mg and 30 mg doses, respectively, the age was 41.9 years and 47.6 years, and disease duration was 8.5 years and 7.1 years. Fecal calprotectin was 4066.9 and 3028.9, respectively, and high sensitivity C-reactive protein levels were 6.2 mg/L and 9.5. There were more patients on corticosteroids in the 15 mg arm at baseline (47.1%) versus the 30 mg dose (38.5%). Other characteristics were similar, including adapted Mayo score (6.8 and 7.0), IBDQ total score (119.3 and 128.1), and FACIT-F score (30.9 and 30.5).

At 52 weeks for those in the 16-week induction group, 26.5% of those in the 15 mg maintenance dose of upadacitinib were in clinical remission as were 43.6% of those in the 30 mg arm. In the full population of the study, the clinical remission rates at week 52 were 10.8%, 40.4%, and 53.6% for those in the placebo, 15 mg, and 30 mg arms, respectively.

Of the 16-week responders, 78.1% of those in the 30 mg upadacitinib arm maintained response through the maintenance period. In the 15 mg arm, 49.1% of patients maintained a response. No abdominal pain at week 52 was experienced by 48.7% and 38.2% of those in the 30 mg and 15 mg arms, respectively, and there was also no bowel urgency for 59% and 32.4%, respectively.

Endoscopic improvements at 52 weeks were experienced by 51.3% with 30-mg upadacitinib and by 34.3% with the 15 mg dose. Endoscopic remission was experienced by 17.9% and 12.2% of patients in the 30 mg and 15 mg doses, respectively. Histologic-endoscopic mucosal improvements were seen in 41.0% of patients treated with 30-mg upadacitinib and by 21.9% of those in the 15 mg arm. Mucosal healing was similar between groups (12.8% and 12.0%).

One or more adverse event (AE) was experienced by 57.1% of those in the 15 mg arm and by 65.0% of those in the 30 mg group. Serious AEs were experienced by 2.9% of those in the smaller dose compared with in 10% of those at the larger dose. AEs led to discontinuation for 2.9% of patients in the 15 mg arm and for 5.0% in the 30 mg dose.

Serious infections were seen in 2.9% of patients in the 15 mg arm and by 5.0% in the 30 mg arm. Other events of special interest in the 15 mg and 30 mg arms, respectively, included herpes zoster (0% and 5.0%), non-melanoma skin cancer (0% and 2.5%), adjudicated major adverse cardiovascular event (0% and 2.5%), anemia (5.7% and 7.5%), and neutropenia (0% and 5.0%).

"Upadacitinib maintenance therapy demonstrated an acceptable safety profile with no new safety signals," said Loftus. "Selected AEs of special interest were reported infrequently with both maintenance doses."

The oral abstract, “Efficacy and Safety of Upadacitinib in Patients with Moderately to Severely Active Ulcerative Colitis Receiving 16 Weeks’ Extended Induction Treatment Followed by 52 Weeks’ Maintenance Treatment in the U-ACHIEVE/U-ACCOMPLISH Trials,” was presented at ACG 2022.