Frequency of Tofacitinib-Linked Malignancy Events in Ulcerative Colitis

A colon affected by ulcerative colitis.
A colon affected by ulcerative colitis.
Researchers analyzed malignancy events and their relationship to tofacitinib treatment levels in patients with ulcerative colitis.

Patients with ulcerative colitis treated with tofacitinib may have similarly infrequent malignancy events to patients with rheumatoid arthritis or psoriatic arthritis treated with tofacitinib, and to patients with ulcerative colitis treated with biologic treatments, according to study results published in Inflammatory Bowel Diseases.

A team of investigators conducted an integrated analysis of 2 phase 3 induction studies, a phase 3 maintenance study, and an ongoing, open-label, long-term extension study ( Identifiers: NCT01465763NCT01458951NCT01458574, and NCT01470612) from the tofacitinib phase 3 ulcerative colitis development program. They aimed to further highlight safety profiles of tofacitinib use in patients with ulcerative colitis. Additionally, they evaluated the relationship between malignancy events and average daily dose levels, changes over time, and possible risk factors that may lead to malignancy predispositions.

As of May 27, 2019, 1124 patients who received at least 1 dose of tofacitinib (5 mg or 10 mg twice daily) were included in the analysis. Exposure was 2576.4 patient-years (mean, 837.2 days). Due to study design, 82% of patients received the 10 mg twice daily dose.

Excluding nonmelanoma skin cancer, 20 patients had recorded malignancies as of May 2019, and the overall incidence rate for all patients treated with tofacitinib in the ulcerative colitis clinical development program was 0.75 per 100 patient-years. Of the 20 patients with malignancies, 17 patients were treated with 10 mg tofacitinib twice daily; the incidence rate among this subgroup was 0.86 per 100 patient-years. The other 3 patients were administered 5 mg tofacitinib twice daily and had an incidence rate of 0.44 per 100 patient-years. Malignancy types varied and no significant type clusters were observed.

Of the 4 deaths reported among patients treated with 10 mg twice daily tofacitinib, 3 patients died due to malignancy, while 1 patient died due to pulmonary embolism. A stable interval of overall incidence rates of malignancies (excluding nonmelanoma skin cancer) was observed in 6-month intervals with an incidence rate of 0.41 per 100 patient-years in the first 6 months and an incident rate of 0.65 per 100 patient-years at more than 30 months.

While intervals were stable, a trend towards an increasing risk for malignancy was observed in the overall cohort in patients with previous treatment and/or lack of treatment response to thiopurines or tumor necrosis factor inhibitors compared against patients without such treatments.

“Before initiation of tofacitinib treatment, the risks and benefits of tofacitinib should be

considered in patients with known malignancies other than successfully treated [nonmelanoma skin cancer], or when considering continuation of tofacitinib treatment in those patients who develop a malignancy,” the authors concluded.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Lichtenstein GR, Rogler G, Ciorba MA, et al. Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancy (excluding nonmelanoma skin cancer) events across the ulcerative colitis clinical program. Inflamm Bowel Dis. 2021;27(6):816-825. doi: 10.1093/ibd/izaa199