Effects of Tofacitinib, an Oral Janus Kinase Inhibitor, on Active Ulcerative Colitis
This multi-center, phase 2 clinical trial was conducted on 194 patients ≥ 18 years with a diagnosis of ulcerative colitis for at least 3 months. Over 8 weeks, the active ulcerative colitis patients were treated with twice-a-day 0.5 mg to 15 mg of tofacitinib or placebo. The main outcome was a reduction in ulcerative colitis activity and rectal bleeding as per the Mayo score, which measures the disease severity on a 0-12 scale. Patients continued to receive oral mesalamine or prednisone daily. Colonoscopy was conducted at 0 and 8 week time-points.
The study results showed that after 8 weeks, ulcerative colitis activity decreased by 32%, 48%, 61%, and 78% in patients treated with 0.5 mg, 3 mg, 10 mg and 15 mg tofacitinib, respectively. A 42% decrease in ulcerative colitis activity was also observed in placebo-treated patients. On the other hand, clinical remission was seen in 13%, 33%, 48%, and 41% of patients receiving 0.5 mg, 3 mg, 10 mg and 15 mg tofacitinib, respectively, while 10% placebo-treatment patients showed clinical remission.
Common serious side-effects of tofacinitib included influenza and nasopharyngitis. Other side effects were a decrease in neutrophil count (a type of white blood cell) and increase in LDL-cholesterol levels.
In conclusion, patients with active moderate or severe ulcerative colitis treated with high doses tofacitinib had a clinical response and clinical remission more frequently than those receiving placebo. The role of tofacitinib in maintenance therapy has not been established. Larger studies are required to establish the benefits and adverse effects of tofacitinib in active ulcerative colitis.
Reference: Tofacitinib, an Oral Janus Kinase Inhibitor, in Active Ulcerative Colitis; William Sandborn et al; N Engl J Med 2012; 367:616-624