Upadacitinib Meets Primary, All Ranked Secondary Endpoints in Ulcerative Colitis Study

AbbVie announced positive results from the Phase 3 induction study, U-ACHIEVE, which showed upadacitinib (45 mg, once daily) met the primary endpoint of clinical remission (per Adapted Mayo Score) at week 8, as well as all ranked secondary endpoints, in adult patients with moderate to severe ulcerative colitis. In the study, 26 percent of patients receiving upadacitinib achieved clinical remission compared to 5 percent of patients receiving placebo (p<0.001). U-ACHIEVE is the first of two Phase 3 induction studies to evaluate the safety and efficacy of upadacitinib in adults with moderate to severe ulcerative colitis.

"Despite the availability of multiple treatment options with varying mechanisms of action, many patients still do not achieve disease control," said Michael Severino, M.D., vice chairman and president, AbbVie. "We are encouraged by these results showing upadacitinib's potential to improve clinical, endoscopic and histologic outcomes in patients with ulcerative colitis."

Significantly more upadacitinib-treated patients achieved endoscopic improvement at week 8 compared to patients receiving placebo (36 percent versus 7 percent; p<0.001). Furthermore, 30 percent of patients treated with upadacitinib achieved histologic-endoscopic mucosal improvement at week 8, versus 7 percent of those receiving placebo (p<0.001). A greater proportion of patients treated with upadacitinib achieved clinical response (per Adapted Mayo Score) at week 8 compared to placebo (73 percent versus 27 percent; p<0.001), and 60 percent of upadacitinib-treated patients experienced clinical response (per partial Adapted Mayo Score) at week 2, versus 27 percent on placebo (p<0.001).

"Ulcerative colitis is a complex disease to manage, and many patients do not achieve relief from symptoms," said Silvio Danese, M.D., lead study investigator and head of the Inflammatory Bowel Diseases Centre at Humanitas Research Hospital, Milan, Italy. "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."

The safety profile of upadacitinib (45 mg) was consistent with safety findings in previous studies across indications, with no new safety risks observed.1-5 During the 8-week study period, the most common adverse events (AEs) observed in the upadacitinib group were acne, blood creatine phosphokinase increase and nasopharyngitis.1 The increases in blood creatine phosphokinase were non-serious and did not lead to study drug discontinuation. Patients with blood creatine phosphokinase increase were usually asymptomatic and no cases of rhabdomyolysis were reported.  Serious adverse events (SAEs) occurred in 2.5 percent of patients in the upadacitinib group and 5.8 percent of patients in the placebo group. Serious infections were reported infrequently (1.6 percent in the upadacitinib group and 1.3 percent in the placebo group). No deaths, gastrointestinal perforation, malignancy, major cardiovascular or thromboembolic events were reported.

Full results from the U-ACHIEVE study will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal. Use of upadacitinib in ulcerative colitis is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

Ulcerative colitis is a chronic, systemic, inflammatory disease caused by inflammation of the large intestine, which triggers abdominal pain, bloody diarrhea, severe urgency for a bowel movement, weight loss and fatigue. The severity of symptoms and uncertainty surrounding flares cause a substantial burden and often disability among those living with the disease.