Low rate of C. difficile infection in UC patients on tofacitinib
The incidence of Clostridium difficile (C. difficile) infection among patients with ulcerative colitis (UC) who are receiving treatment with tofacitinib is low and particularly so when compared with C. difficile infection incidence in patients receiving other UC therapies, according to a poster presented at AIBD 2018.
“In the tofacitinib UC program, C. difficile infection rates among patients receiving tofacitinib were similar to or lower than those observed with placebo,” said the researchers.
Researchers assessed the incidence of C. difficile infection (be it as an adverse event [AE], C. difficile colitis, or positive test for C. difficile infection plus treatment with vancomycin or metronidazole), in patients in all three cohorts of the tofacitinib UC program – the induction cohort where patients received tofacitinib 10 mg twice/day (n=938) or placebo (n=282) for 8 weeks; the maintenance cohort where patients received tofacitinib 5 mg or 10 mg twice/day (n=394) or placebo (n=198) for 52 weeks; and the overall cohort (n=1,157) comprising all the patients in the induction and maintenance cohorts who received tofacitinib as well as those receiving the drug in an ongoing, open-label, extension study. Patients who tested positive for C. difficile infection during pre-trial screening were excluded.
The incidence of C. difficile infection among patients on tofacitinib was compared with that of patients in a retrospective cohort study which used data obtained from the Truven MarketScan® Database who were receiving other treatments for moderate-to-severely active UC and had also been diagnosed and had a prescription for oral therapy (within 14 days of diagnosis) to treat C. difficile infection (eg, metronidazole, vancomycin, fidaxomicin).
C. difficile infection occurred in three patients in the induction cohort of the tofacitinib UC program, one and two in placebo and tofacitinib recipients, respectively, while all three patients with C. difficile infection in the maintenance cohort were in the placebo group. [AIBD 2018, abstract P035]
The incidence rate (IR) of C. difficile infection in the overall cohort was 0.48 (95 percent confidence interval [CI], 0.21–0.95), with eight patients diagnosed with C. difficile infection over 1,664 patient-years of follow up; two cases were deemed serious AEs. All cases of C. difficile infection were successfully treated. Six patients opted to continue tofacitinib, while one each temporarily and permanently discontinued tofacitinib.
A total of 160 incidents of C. difficile infection occurred over 4,918 patient-years of follow up in the retrospective cohort study (IR, 3.25, 95 percent CI, 2.77–3.80), of which 116 cases were C. difficile infection-associated hospitalizations over 4,936 patient-years of follow up. Compared with those receiving tofacitinib, the incidence of C. difficile infection was higher among those receiving azathioprine (IR, 3.23, 95 percent CI, 2.18–4.62), 6-mercaptopurine (IR, 2.31, 95 percent CI, 1.26–3.87), and tumour necrosis factor inhibitors (IR, 3.58, 95 percent CI, 2.95–4.29).
“Patients with inflammatory bowel disease [IBD], particularly UC, have a higher risk of C. difficile infection than the general population,” said the researchers. “The incidence of C. difficile infection is increasing among patients with IBD, and certain UC treatments may be associated with greater risk.”
“[In this study], the IR among patients receiving tofacitinib was numerically lower than those observed for immunomodulators and tumour necrosis factor inhibitors in the Truven Cohort,” the researchers pointed out.