By Kirsty Oswald, MedWire Reporter
Tofacitinib can induce a clinical response in the majority of patients with moderate to severe, active ulcerative colitis (UC), a placebo-controlled trial has shown.
Reporting in The New England Journal of Medicine, the authors found that over three-quarters of patients who received tofacitinib 15 mg twice daily responded to treatment.
The majority of patients in the trial had not responded to conventional therapy, and could ultimately require colectomy when they have exhausted medical therapy.
"Treatment options for these patients are limited, and the possibility of an entirely new treatment option is exciting," lead author, William Sandborn (University of California, San Diego, USA), told MedWire News.
The study included 194 patients who were randomly assigned to receive placebo or tofacitinib at one of four twice-daily doses (0.5, 3, 10, or 15 mg) for 8 weeks. Across all the groups, 68% received concomitant aminosalicylates, and 44% received glucocorticoids at some point during the study.
At a dose of 15 mg twice daily, 78% of patients showed a clinical response, defined as an absolute decrease in Mayo score of at least 3 points, and a relative decrease of 30%, as well as a decrease in the rectal bleeding subscore by at least 1 point, or a drop to 0 or 1 point. This was significantly higher in comparison to 42% of patients in the placebo group.
Furthermore, clinical remission - defined as a total Mayo score of 0-2 points with no subscore greater than 1 point - was also achieved in significantly more patients in the 10 mg and 15 mg groups compared with placebo. In all, 41% of patients in the 15 mg and 48% in the 10 mg groups achieved remission compared with only 10% in the placebo group.
Patients in the 15 mg group also showed significant improvements over placebo-treated patients for endoscopic outcomes, C-reactive protein concentrations, fecal calprotectin concentrations, and Inflammatory Bowel Disease Questionnaire scores.
While the number of serious and adverse events was not significantly greater in the treatment groups compared with placebo, the authors noted that dose-responsive increases in low-density lipoprotein and high-density lipoprotein cholesterol and the suppression of neutrophil count in three patients require further study.
"The preliminary short-term safety results from our study are generally comparable to steroids, immunosuppressives, and anti-[tumor necrosis factor] TNF agents. However, we need large long-term trials to better understand the safety profile of tofacitinib in patients with UC," said Sandborn.
Tofacitinib, a janus kinase inhibitor, has previously shown efficacy in preventing organ allograft rejection, and in the treatment of rheumatoid arthritis, and psoriasis. The authors say it could now provide a much-needed treatment option for UC patients who do not respond, or experience severe side effects, from current treatments, such as mesalamine, azathioprine, and TNF inhibitors.
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