Induction treatment with upadacitinib (Rinvoq) provided rapid symptom relief from day 1 for patients with moderate to severe ulcerative colitis, according to a post-hoc analysis of the phase III U-ACHIEVE and U-ACCOMPLISH trials.
In an intention-to-treat analysis involving 988 patients, those who received a daily dose of 45 mg of the JAK inhibitor experienced significant improvements in all ulcerative colitis symptoms, including abdominal pain, stool frequency, rectal bleeding, and bowel urgency at 1 to 3 days compared with placebo, which was maintained through 14 days (P<0.05 for all), reported Edward V. Loftus Jr., MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues.
Significantly more upadacitinib patients also achieved clinical remission (26.9% vs 4.3% of placebo patients) and clinical response (59.4% vs 22.3%, respectively) at 2 weeks, which was maintained through 8 weeks (P<0.001 for all), they noted in Clinical Gastroenterology and Hepatology.
Furthermore, >50% reductions from baseline in high-sensitivity C-reactive protein (hs-CRP) and fecal calprotectin (FCP) levels were achieved by 75.7% and 48.2% of upadacitinib patients compared with 21.9% and 20.2% of placebo patients, respectively (P<0.001 for both).
At 2 weeks, systemic and intestinal inflammation normalized in more upadacitinib patients than placebo patients:
- hs-CRP ≤5 mg/L: 83.1% vs 51.1%
- FCP <150 mg/kg: 30% vs 5%
- FCP <250 mg/kg: 37% vs 10%
“Importantly, these effects were seen regardless of prior biologic exposure,” Loftus told MedPage Today. “Such rapid improvements beg the question if in the future we need to use corticosteroids as a short-term bridge for patients flaring with ulcerative colitis, and instead use a rapidly acting agent such as upadacitinib.”
“It also raises the question as to whether upadacitinib should be employed for patients with acute severe ulcerative colitis,” he added.
Commenting on the study, Dana J. Lukin, MD, PhD, of Weill Cornell Medicine in New York City, told MedPage Today that “these intriguing results help to inform the use of this agent in patients requiring rapid symptom improvement.”
Upon finding similar response rate differences when stratified by baseline corticosteroid use, prior biologic experience, Adapted Mayo score, and disease severity, Loftus and colleagues said this indicated “that these factors did not influence clinical remission rates” between groups. A subgroup analysis that stratified patients by the same factors also found no difference between clinical response rates per Partial Adapted Mayo score, with some starting to plateau at 2 weeks.
Patients with ulcerative colitis often experience recurring bowel urgency, diarrhea, rectal bleeding, and abdominal pain. While corticosteroids can provide rapid symptom improvement for those requiring hospitalization, an unmet need remains for ambulatory patients with moderate to severe disease who may experience a high symptom burden, Loftus and team noted. Variable prolonged response times have been reported with the use of immunosuppressants or biologic therapies, and some patients may even develop loss of response to or treatment failure with such interventions.
In both the U-ACHIEVE and U-ACCOMPLISH trials, those who received upadacitinib met the primary endpoint of clinical remission, assessed by Adapted Mayo score, versus placebo, as well as all secondary endpoints. These two induction trials, along with the U-ACHIEVE Maintenance trial, led to the approval of upadacitinib in March for the treatment of adults with moderate to severe ulcerative colitis who had an inadequate response/intolerance to a tumor necrosis factor blocker.
For this post-hoc analysis, Loftus and colleagues pooled data on 988 patients ages 16 to 75 who received a daily dose of 45 mg of upadacitinib (n=660) or placebo (n=328) from the two induction trials. Participants had an Adapted Mayo score of 5 to 9, an endoscopic subscore of 2 to 3, and had failed or had an inadequate response/intolerance to prior therapies.
Median age was 41-42, and 38% were women. Clinical characteristics were well balanced between groups. About half had failed or had an inadequate response to prior biologics.
In order to determine the earliest time of efficacy, they analyzed patients’ electronic diary entry data after the first dose to assess daily symptom improvement for 14 days.
At weeks 2 and 8, significant improvements in quality of life were seen among patients who received upadacitinib, as assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue, the Ulcerative Colitis Symptoms Questionnaire, the Inflammatory Bowel Disease Questionnaire, the Work Productivity and Activity Impairment questionnaire, the Short Form 36, and the European Quality of Life-5 Dimensions 5 Levels Index Score.
This study was supported by AbbVie.
Loftus reported relationships with AbbVie, Amgen, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Calibr, Celgene, Eli Lilly, Fresenius Kabi, Genentech, Gilead, Gossamer Bio, Iterative Scopes, Janssen, Morphic Therapeutics, Ono Pharma, Robarts Clinical Trials, Receptos, Protagonist, Pfizer, Scipher Medicine, Surrozen, Sun Pharma, Takeda, Theravance, and UCB.
Co-authors also reported multiple relationships with industry.