Reviewed by Dr. Josephine Thinwa
Sandborn, William J., et al. New England Journal of Medicine 376.18 (2017): 1723-1736

This study is a compilation of 3 double blind placebo-control trials meant to determine the efficacy of tofacitinib, a JAK inhibitor, as induction or maintenance therapy for ulcerative colitis (UC). Tofacitinib was previously shown in a phase 2 trial to have some efficacy as induction therapy for UC. For this study, the target population was patients with moderate to severe UC who have failed conventional therapy or tumor necrosis factor (TNF) antagonists. The goal was to see if remission could be achieved after 8 or 52-weeks of therapy. In the 8-week trial, remission was achieved in 18.5% versus 8.2% in the placebo group. For the 52-week trial, patients were either given 5 mg or 10 mg of tofacitinib. Remission was achieved in 34.3% with 5 mg and 40.6% with 10 mg, compared to 11.1% in the placebo arm. All these differences were statistically significant. Furthermore, compared to placebo, patients on tofacitinib had slightly higher rates of herpes infection, non-melanoma skin cancer, hyperlipidemia, and cardiovascular events.

Ulcerative colitis (UC) is a serious illness that is characterized by abdominal discomfort and bloody diarrhea. A large number of patients do not achieve remission with conventional therapy or with antagonist to TNF α, and have to consider colectomy with its associated morbidity. Tofacitinib is a relatively new drug that has shown promise either as induction or maintenance therapy for patients with moderate to severe UC. Tofacitinib works as a small molecule inhibitor of Janus Kinases (JAK), which play a role in inflammatory responses. Specifically, JAK proteins are involved in the JAK-STAT signal transduction pathways that are activated by cytokines in order to affect lymphocyte differentiation, function and proliferation. The FDA already approved tofacitinib for the treatment of rheumatoid arthritis 5 years ago. In this study, UC patients on tofacitinib achieved significantly higher rates of remission in a dose- and time-dependent manner when compared to placebo. Since this was a placebo trial, it is unclear how efficacious tofacitinib is compared to conventional therapy or TNF α antagonists. It is possible that even higher rates of remission could be achieved with the use of tofacitinib as an adjunct therapy, an area that warrants further investigation.