Ulcerative colitis is a long-term
inflammatory disorder of the large intestine (colon) and rectum. There is no
effective therapy which works in all patients of ulcerative colitis. In a
recent study, tofacitinib (CP-690,550), a selective Janus kinases inhibitor was
evaluated for its effectiveness against ulcerative colitis. By blocking Janus
kinases, the drug inhibits the
inflammatory process of 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
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
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