Previous analysis of the tofacitinib ulcerative colitis (UC) clinical program has shown clostridium difficile infection (CDI) rates among patients receiving tofacitinib to be similar or lower than patients treated with placebo, immunomodulator, or TNFi.
An updated analysis of program’s results as of May 2019 demonstrated that CDI rates have remained stable and generally infrequent in this population over time.
These results were presented at the annual American College of Gastroenterology (ACG) 2020 conference.
A team led by Edward Loftus, Jr., MD, of Mayo Clinic of Medicine, Minnesota, evaluated CDI events from 4 randomized, placebo-controlled studies. These included Phase 2 and Phase 3 induction studies, a maintenance Phase 3 study, and an ongoing open-label, long-term extension study.
All enrolled patients in the program had undergone CDI screening, and anyone with a positive CDI test were excluded from it.
For the team’s analysis, the studies were grouped into 3 cohorts—Induction, Maintenance, and Overall. The Overall cohort included all patients who received ≥1 dose of tofacitinib. Placebo-exposed patients were not included in this cohort.
Thus, a total of 1157 patients were included in the Overall cohort. These patients received either 5 mg or 10 mg of the investigative drug twice daily. This population represented 2581 patient-years of exposure and up to 6.8 years of treatment.
Furthermore, CDI occurred in 9 patients in the cohort. These events occured in those on 10 mg of tofacitinib dosage.
These CDI incidences were either mild (n = 4) or moderate (n = 5) in severity. Additionally, 6 of these patients continued study treatment without interruption, 1 temporarily discontinued treatment, and 2 permanently discontinued treatment. Only 1 was in hospital at the time of CDI, and 1 had prior history of CDI.
The investigators reported that CDI resolved with treatment in 8 patients, and CDI was still present in 1 patient at time of discontinuation.
Furthermore, 2 events were reported as serious adverse events.
Within the induction cohort—which only represented 8 weeks of treatment— 2 patients receiving 10 mg twice-daily tofacitinib (n = 938) experienced CDI, compared with 1 patient in the placebo group (n = 282).
None of the patients had any prior history of CDI nor were hospitalized at time of infection. CDI was resolved in both patients from the tofacitinib group and was ongoing in the placebo-treated patient at the study’s end as well as follow-up.
In the maintenance cohort, total CDI occurred in 3 patients who were part of the placebo-group. They had received 10 mg of tofacitinib twice-daily during induction, but experienced CDI following initiation of placebo. Only 1 patient had prior history of CDI, and none were hospitalized at time of CDI.
CDI resolved in 2 patients and was considered ongoing in 1.
“In the tofacitinib UC program, CDI rates among patients receiving tofacitinib have remained stable since the previous data cut and are comparable to those reported for other advanced therapies and the general population,” Loftus and colleagues wrote.