Tofacitinib upped herpes zoster risk in ulcerative colitis

Worsening ulcerative colitis was the most common serious adverse event for patients who received both induction and maintenance therapy. For patients on maintenance therapy, only herpes zoster infection had a higher incidence than placebo, which reached statistical significance at the 10-mg dose. These safety findings resemble those in rheumatoid arthritis trials of tofacitinib, and apart from herpes zoster, they also resemble safety data for vedolizumab (an integrin receptor antagonist), and anti-tumor necrosis factor agents in ulcerative colitis, the researchers wrote.

There were four deaths during the entire tofacitinib ulcerative colitis program, for an incidence rate of 0.2 per 100 person-years of exposure. All occurred in patients receiving 10 mg twice daily. Causes of death were dissecting aortic aneurysm, hepatic angiosarcoma, acute myeloid leukemia, and pulmonary embolism in a patient with cholangiocarcinoma that had metastasized to the peritoneum. Recently, concerns about pulmonary embolism have led the European Medicines Agency (EMA) to recommend against the use of 10-mg twice daily tofacitinib dose in patients at increased risk for pulmonary embolism.

“Compared with prior experience with tofacitinib in rheumatoid arthritis, no new or unexpected safety signals were identified,” the researchers concluded. “These safety findings support the long-term use of tofacitinib 5 and 10 mg twice daily in patients with moderately to severely active” ulcerative colitis.

Pfizer makes tofacitinib, funded the individual trials, and paid for medical writing. Dr. Sandborn disclosed grants, personal fees, and nonfinancial support from Pfizer and many other pharmaceutical companies.

SOURCE: Sandborn WJ et al. Clin Gastroenterol Hepatol. 2018 Nov 23. doi: 10.1016/j.cgh.2018.11.035.