Adverse Events Similar Between JAK Inhibitor Xeljanz and Biologics After Colectomy in UC Patients, Study Finds

Xeljanz (tofacitinib) is an oral, small molecule Janus kinase (JAK) inhibitor FDA-approved for the treatment of several inflammatory autoimmune conditions, including ulcerative colitis (UC). Xeljanz was the first in its class approved to treat moderate-to-severe UC.

Like other JAK inhibitors, tofacitinib carries a boxed warning for the increased risk of thrombosis, including venous thromboembolism (VTE), pulmonary embolism, and arterial thrombosis. This warning is based on results from previous studies of people with rheumatoid arthritis receiving JAK inhibitors. However, this risk has not been confirmed in patients with inflammatory bowel disease (IBD), especially when comparing tofacitinib with other small molecules and biologics.

The emergence of biologics and other disease-modifying therapies for UC has changed the face of UC treatment in the last 20 years. However, although the number is decreasing, up to 15% of patients with UC will still require colectomy surgery during their lifetime.

Considering the existing boxed warning, there have been concerns regarding the need for a pre-surgery washout period for people with UC who are receiving tofacitinib. However, delaying surgery may result in an increased risk of morbidity, lengthened hospital stays, and increased costs.

To evaluate the risk of postoperative complications associated with tofacitinib exposure before colectomy compared to biologic exposure, Gabriele Dragoni, M.D., Ph.D., from the IBD Referral Centre at Careggi University Hospital in Florence, Italy, and her colleagues conducted a multicenter, retrospective, observational study of patients with UC undergoing a total colectomy due to treatment-resistant disease.

The study results were published this month in the American Journal of Gastroenterology.

Participants included patients with active UC who were taking immunosuppressive treatments and were referred for total colectomy between September 2005 and February 2023. Immunosuppressive treatments included tofacitinib, three tumor necrosis factor (TNF) inhibitors (infliximab, adalimumab, and golimumab), vedolizumab, and ustekinumab.

The study included patients who received the last dose of tofacitinib within four weeks before colectomy and the last dose of any biologic within 12 weeks before surgery. The patients were divided into four groups based on whether they took tofacitinib, vedolizumab, ustekinumab, or a TNF inhibitor before surgery.

The primary outcome was the occurrence of any post-surgery complications within 30 days (early) and 90 days (late) after surgery between patients who took tofacitinib and those who took a biologic before surgery.

The researchers analyzed the records of 301 patients. Of those, 64 (21.3%) were in the tofacitinib group, and 237 used biologics. From the biologics group, 162 (53.8%) used a TNF inhibitor, 54 (17.9%) used vedolizumab, and 21 (7%) used ustekinumab.

A total of 29.9% of patients had at least one early complication, and 8.5% had at least one late complication. There were no significant differences between the tofacitinib group and the other three groups regarding early or late complications, infections, or sepsis.

No VTEs were reported for the tofacitinib group, compared to an increased risk of early VTE seen in the TNF inhibitor group and late VTE seen in the vedolizumab group.

Dragoni and her colleagues concluded that postoperative adverse events for tofacitinib and biologics are similar in patients with UC undergoing colectomy due to treatment-resistant disease. They recommend larger prospective studies to confirm their results.