During the induction period, patients in the treatment group had higher incidences of infections and serious infectious compared to placebo.
William Sandborn, MD
Investigators believe the results of a phase 2 study warrant future research testing upadacitinib in patients with Crohn’s disease.
A team, led by William J. Sandborn, MD, Division of Gastroenterology, University of California San Diego, evaluated the efficacy and safety of upadacitinib in patients with Crohn’s disease.
In the randomized, double-blind, phase 2 trial, the investigators tested 220 adults with moderate to severe Crohn’s disease who had an inadequate response or intolerance to immunosuppressants or tumor necrosis factor antagonists. Equal amounts of patients received either 3, 6, 12, or 24 mg of the oral selective Janus kinase 1 inhibitor, or a placebo twice daily or 24 mg upadacitinib once daily.
The investigators evaluated patients with a ileoncolonoscopy at weeks 12 or 16 for the induction period. Patients who completed week 16 were then re-randomized to a 36-week period of maintenance therapy with upadacitinib.
The investigators sought primary endpoints of clinical remission at week 16 and endoscopic remission at week 12 or 16 using the multiple comparisons procedure and modeling and the Cochran-Mantel0Haenszel test, with a 2-side level of 10%.
Of the 220 patients, 13% achieved clinical remission receiving 3 mg of the study drug, while 27% of patients receiving 6 mg upadacitinib (P <0.1 vs placebo), 11% of patients receiving 12 mg upadacitinib, and 22% of patients receiving 24 mg upadacitinib twice daily, and by 14% of patients receiving 24 mg upadacitinib once daily, compared to 11% of patients receiving placebo achieved remission.
Endoscopic remission was achieved by 10% (P < .1 vs placebo), 8%, 8% (P < .1 vs placebo), 22% (P < .01 vs placebo), and 14% (P < .05 vs placebo) of patients receiving upadacitinib, respectively, while none of the patients receiving placebo achieved endoscopic remission.
The investigators also found that only endoscopic remission increased with dose during the induction period and efficacy was maintained for most endpoints through week 52.
During the induction period, patients in the treatment group had higher incidences of infections and serious infectious compared to placebo. In addition, patients in the twice daily 12 and 24 mg groups had substantial increases in total, high-density lipoprotein and low-density lipoprotein cholesterol levels compared to the placebo group.
“In a phase 2 trial of patients with CD, upadacitinib induced endoscopic remission in a significant proportion of patients compared with placebo,” the authors wrote. “Upadacitinib’s benefit/risk profile supports further development for treatment of CD.”
Recently, findings presented at the European E-Congress of Rheumatology 2020 (EULAR 2020) meeting, showed higher doses of upadacitinib increase the incidence rate of serious infection events and opportunistic infections in patients with rheumatoid arthritis.
Kevin Winthrop, MD, MPH, from Oregon Health & Science University, and a team of international and US-based investigators, evaluated the incidence of serious infection events and opportunistic infections in patients with rheumatoid arthritis receiving upadacitinib and active comparators in the phase 3 SELECT clinical trial program.
Overall, the incidence rate of serious infection events and opportunistic infections was higher among the upadacitinib 30 mg group than the 15 mg group. The serious infection events seen with the 15 mg group were similar to those seen with adalimumab.
The study, “Efficacy and Safety of Upadacitinib in a Randomized Trial of Patients With Crohn’s Disease,” was published online in Gastroenterology.