Patients with moderately to severely active ulcerative colitis who were treated with the selective oral Janus kinase (JAK) inhibitor tofacitinib were more likely to show clinical response and remission compared with patients given placebo, particularly those given higher doses, according to results of a recent study [N Engl J Med. 2012;367(7):616-624].
Conventional treatments such as mesalamine, glucocorticoids, azathioprine, and anti-tumor necrosis factor agents are not always effective in treating ulcerative colitis, a chronic inflammatory disease of the colon. Tofacitinib, already shown to be effective in preventing organ allograft rejection and in treating rheumatoid arthritis and psoriasis, was the subject of an 8-week, placebo-controlled, dose-finding phase 2 trial conducted by William J. Sandborn, MD, of the University of California San Diego, La Jolla, and his colleagues. (The study’s sponsor, Pfizer, assisted in the study’s design and analysis of the data.)
The study was performed at 51 centers in 17 countries from January 2009 through September 2010. To be eligible, patients had to be at least 18 years of age, have had ulcerative colitis for at least 3 months, have scores of 6 to 12 on the Mayo scale, and have moderate or severe disease as shown by sigmoidoscopy Mayo endoscopic findings (subscore of 2 or 3, respectively). The primary efficacy end point was a clinical response at 8 weeks, with secondary efficacy end points including clinical remission and endoscopic response and remission, all at 8 weeks; and change from baseline in partial and total Mayo scores at 2, 4, and 8 weeks.
Among a total of 194 patients, 48 received placebo; 31, 33, 33, and 49 patients received 0.5, 3, 10, and 15 mg of tofacitinib twice daily, respectively. Colonoscopy or flexible sigmoidoscopy was performed at baseline and again at 8 weeks. After 8 weeks of treatment, follow-up continued for 4 weeks.
The researchers defined a clinical response as a decrease from baseline in the total Mayo score of at least 3 points and a relative decrease by at least 30%, as well as a decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. They defined clinical remission as a total Mayo score of 0 to 2, with no individual subscores above 1.
An endoscopic response occurred if there was a decrease from baseline in the endoscopy subscore by at least 1, and endoscopic remission if the endoscopy subscore was 0. A maximum-effective-dose model was used to analyze the primary end point as well as selected secondary end points. Results are shown in the Table below.