Malignancy events were rare during a phase 3 clinical development program of tofacitinib treatment for ulcerative colitis (UC), according to study results were published in Inflammatory Bowel Disease.
Investigators pulled data from a phase 3 maintenance study and a phase 3 open-label, long-term extension study for this analysis. In the 2 studies, patients with UC were treated with 5 mg (18%) or 10 mg (82%) twice daily of tofacitinib (a small molecule Janus kinase inhibitor) for 8 weeks (induction study, n=1139), 52 weeks (maintenance study, n=592), or up to 6.8 years (ongoing long-term extension study, n=1124).
A total of 20 participants reported malignancies (excluding nonmelanoma skin cancer). The overall incidence rate (IR) was 0.75 (95% CI, 0.46-1.16)/100 PYs. Of the patients with a reported malignancy, 17 received the higher dose of tofacitinib. The malignancies were cholangiocarcinoma, leukemia, lung cancer, essential thrombocythemia, renal cancer, hepatic angiosarcoma, penis cancer, esophageal adenocarcinoma, cutaneous leiomyosarcoma, colorectal cancer, cervical cancer, lymphoma, melanoma, and breast cancer.
Death from the observed malignancies occurred among 4 patients, who each received the 10-mg dose of tofacitinib; 3 of the 4 patients died >28 days after their last tofacitinib dose. The patients died from hepatic angiosarcoma, acute myeloid leukemia, melanoma, and during an endoscopic retrograde cholangiopancreatography treatment for cholangiocarcinoma. The time since first tofacitinib dose was 232, 398, 1518, and 384 days, respectively.
The incidence rate for an occurrence of a malignancy was 0.41 (95% CI, 0.05-1.47)/100 PYs during the first 6 months and increased to 0.65 (95% CI, 0.24-1.41)/100 PYs for >30 months.
Malignancies were more prevalent among patients who had previously been treated with thiopurines (n=13) or a tumor necrosis factor inhibitor (n=19). Patients with increased age (every 10 years; hazard ratio [HR] =1.45; 95% CI, 1.03-2.04) or with longer disease duration (HR=1.05; 95% CI, 1-1.09) were more likely to develop a malignancy.
A limitation of this study was the prevalence of prior exposure to immunosuppressant drugs, which is known to result in long-term risk for malignancies. Prior drug exposures may have skewed these results.
The study authors concluded that malignancies were not common among patients receiving treatment with tofacitinib, even after long-term exposure. Of the observed malignancies, no specific types appeared to be more common, and risk of developing a malignancy was stable over time.
Disclosure: Multiple authors declared industry affiliations. 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 [published online August 7, 2020]. Inflamm Bowel Dis. doi: 10.1093/ibd/izaa199