Results from both studies showed the safety of filgotinib for the treatment of ulcerative colitis compared to placebo treatment groups.
Filgotinib 200 mg and filgotinib 100 mg may be viable treatment options for patients with moderately to severely active ulcerative colitis (UC), according to positive safety profile data from the phase 2b/3 SELECTION study and its long-term extension study SELECTIONLTE.
Integrated safety data from both studies demonstrated the safety of filgotinib independent of previous biologic exposure or age, with safety outcomes remaining consistent across filgotinib 200 mg, filgotinib 100 mg, and placebo treatment groups.1
“For moderately to severely active disease, immunosuppressants and biologics are recommended. Primary failure and/or loss of response to biologics occur in approximately 50% of patients, highlighting the need for effective new drugs with good safety profiles,” wrote investigators.1
Although there is no known cure, treatment for UC aims to induce and maintain remission through medications including immunomodulators, biologics, and janus kinase inhibitors.2 For patients who do not respond to medication, elective or total colectomy may be necessary.3
To assess the safety profile of filgotinib for the treatment of moderately to severely active UC, Stefan Schreiber, MD, director of the department of internal medicine and head of the institute of clinical molecular biology at Kiel University in Germany, and a team of investigators examined integrated safety results from SELECTION and SELECTIONLTE. A phase 2b/3, double-blind, randomised, placebo-controlled trial, SELECTION demonstrated filgotinib 200 mg once daily was well tolerated and effective in inducing and maintaining clinical remission compared to placebo in both biologic-naive and biologic-experienced patients with UC.1
Limiting their analyses to those who completed or met efficacy discontinuation criteria, the current study included 1348 of the 1348 patients within the original SELECTION study. Investigators divided participants into 3 cohorts. Cohort 1 included patients from the SELECTION induction studies A (biologic-naive patients) and B (biologic-experienced patients) who received placebo, filgotinib 100 mg, or filgotinib 200 mg once daily for up to 11 weeks. Cohort 2 included responders to filgotinib induction therapy and responders to induction placebo who were rerandomized to start/continue their filgotinib induction dose or to start/continue placebo in the maintenance study for 47 weeks. Cohort 3 comprised all patients who entered SELECTION and may have participated in the maintenance study and/or in SELECTIONLTE.1
Cohort 1 included 279 patients who received placebo and 1069 patients who received filgotinib with an overall mean age of 43 years, mean UC duration of 8.4 years, and mean MCS of 9.0. In cohort 2, 664 patients who responded to induction treatment and participated in the maintenance study were included. Cohort 3 included 1170 patients treated in SELECTIONLTE, of whom 873 received filgotinib 200 mg, 160 received filgotinib 100 mg, and 137 received placebo.1
For cohorts 1 and 2, follow-up for safety endpoints lasted until March 31, 2020. In cohort 3, which is the ongoing maintenance cohort, the cutoff date for safety endpoints was February 24, 2022. Adverse events of interest included infections, venous thromboembolic events, major adverse cardiovascular events, malignancies, and nonmelanoma skin cancers. Severe adverse events were defined as those of grade 3 or greater. Serious adverse events were defined as those leading to death, immediate risk of death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or a congenital anomaly. Exposure-adjusted incidence rates (EAIRs) per 100 censored patient-years of exposure were reported overall by treatment group in cohort 3.1
Upon analysis, the overall EAIR for filgotinib 200 mg was 37.07. Serious adverse events occurred at a low frequency across treatment groups (EAIR 7.94 for filgotinib 200 mg, 9.62 for filgotinib 100 mg, and 9.00 for placebo). The EAIR for all adverse events was similar for filgotinib 100 mg (167.39) and placebo (166.65), and numerically lower for filgotinib 200 mg (122.96). The EAIR of adverse events leading to hospitalization and discontinuation of study drug were similar across treatment groups. 1
The EAIR for herpes zoster was 1.44 in patients receiving filgotinib 200 mg, 0.69 in patients receiving filgotinib 100 mg, and 0.26 in patients receiving placebo. Among patients aged 65 years or older treated with filgotinib 200 mg and filgotinib 100 mg, the EAIR was numerically greater (2.93 and 3.37, respectively) than in younger patients (1.32 and 0.54, respectively), although investigators pointed out this was expected due to increased susceptibility to herpes zoster with increasing age.1
Further analysis revealed the EAIR for major adverse cardiovascular events was reduced across all treatment groups (0.31 for filgotinib 200 mg, 0.35 for filgotinib 100 mg, and 0.52 for placebo). When assessed by age subgroup, patients 65 years of age or older who received filgotinib 200 mg or filgotinib 100 mg had an increased EAIR for major adverse cardiovascular events (EAIR 1.73 and EAIR 3.37, respectively) compared to younger patient groups (EAIR 0.19 for filgotinib 200 mg and 0.18 for filgotinib 100 mg). Of note, the EAIR of all infections was greater in those 65 years of age or older than in younger patients across treatment groups.1
In addition to increased age, investigators pointed out the EAIR of all infections was consistently greater among biologic-experienced patients and patients in whom biologic therapy had failed than in biologic-naive patients and patients in whom biologic therapy had not failed, highlighting the role of uncontrolled UC in driving infections. Of note, none of the 4 deaths in the studies were considered related to filgotinib.1
“This integrated safety analysis of data from SELECTION and SELECTIONLTE demonstrated that FIL was well tolerated and had an acceptable safety profile in patients with moderately to severely active UC, independent of previous biologic exposure or age,” concluded investigators.1