Ulcerative colitis is a chronic inflammatory disease that affects the rectum and may affect part or the entire colon.

On the occasion of the thirteenth edition of the ECCO (European Crohn’s and Colitis Organization) congress held in Vienna from 14 to 17 February, Professor Silvio Danese, Head of the Centre for Chronic Bowel Diseases at Humanitas, Professor at Humanitas University and President of ECCO, showed partial results from a phase 2 study, which showed that treatment with apremilast was effective in inducing clinical and endoscopic improvements in patients with active ulcerative colitis who had failed at least one conventional therapy and who had never been treated with biological therapy.

The results show that a higher percentage of patients treated with apremilast manage to achieve clinical remission than placebo and as professor Danese explains: “Achieving clinical remission, which requires endoscopic improvement of the mucosa, is a significant goal in the treatment of ulcerative colitis”.

 

What is apremilast and how does it act?

Apremilast is a small molecule that is administered orally and that is able to inhibit phosphodiesterase-4 (PDE4), an enzyme that through its intracellular action regulates pro and anti-inflammation modulators in ulcerative colitis and other inflammatory diseases. Inhibiting PDE4, apremilast increases the anti-inflammatory activity compared to the pro-inflammatory one.

This molecule has already received approval for the treatment of psoriatic arthritis (spondyl arthritis psoriatic) and to treat psoriatic plaques and it is currently being studied for the treatment of other diseases such as ulcerative colitis.

 

The study

The study (double-blind, control-placebo) evaluated the safety and efficacy of apremilast in patients with active ulcerative colitis (with Total Mayo Endoscopic Score (TMS) between 6 and 11 and Mayo Endoscopic Score (MES) equal to or greater than 2) in whom at least one conventional course of therapy had failed and who had never been treated with biological therapy.

The 170 patients involved were randomly divided to receive 30 mg apremilast (57 patients), 40 mg apremilast (55 patients) and placebo (58 patients) for 12 weeks, during which time their histological and endoscopic score was calculated. The results presented at the ECCO congress related to these first 12 weeks, as the study was still ongoing. The study was completed by 87% of placebo-treated patients, 93% of those with 30 mg of the molecule and 94.5% of those who had taken 40 mg apremilast.

The main objective was the proportion of patients with a clinical remission calculated with a total mean score of 2 or less.

Remission was achieved by 31.6% of patients receiving 30 mg of the drug, 21.8% of those receiving 40 mg and 13.8% of those receiving placebo.

There was also a significant decrease in reactive C protein over 12 weeks in both groups treated with apremilast compared to the placebo group, and a decreasing trend was also observed for fecal calprotectin.

“These findings suggest that apremilast, which improved the likelihood of achieving remission in this 12-week study, deserves further study in a larger trial,” concluded Professor Danese.