ART trial: Adacolumn shows clinical benefit in refractory ulcerative colitis patients

Data from the 48-week ART trial, presented today at the Digestive Disease Week (DDW) meeting, showed that remission and response rates were 37.2% and 53.2% respectively at week 12, in patients with moderate-to-severe, steroid-dependent active ulcerative colitis (UC) with insufficient response or intolerance to immunosuppressants and / or biologics when treated with between five and eight sessions with Adacolumn^®.

Adacolumn^® is a non-pharmacological treatment which reduces inflammation by removing white blood cells from the blood circulation. This reduces the inflammatory burden without the risk of side effects attributed to drugs in patients with inflammatory bowel disease (IBD), such as active UC.

UC is associated with an imbalance of white blood cells known as leukocytes (granulocytes / monocytes), which play a key role in inflammation. In UC, these inflammatory cells migrate into the intestinal mucosa at twice the normal levels causing mucosal inflammation. Targeting leukocytes or their communication is the rationale behind most IBD treatments.

UC is a chronic relapsing and remitting inflammatory condition of the colon affecting up to 246 people per 100,000 population. Relapses present with symptoms such as abdominal pain, bloody diarrhoea, weight loss and anaemia, all of which have a significant impact on quality of life.

Prof. Dr. Axel Dignass, Agaplesion Markus Hospital, Frankfurt, Germany, said:

Ulcerative colitis is a debilitating disease with increasing prevalence and affects many young people. Ultimately, the goal of our treatment is to induce steroid-free clinical remission. However, patients with moderate to severe ulcerative colitis and their healthcare professionals are faced with many hard choices, particularly when it comes to choosing the best treatment, since many have side effects that severely impact quality of life and may even be life-threatening.

The ART data have shown that there is an alternative for this difficult-to-treat population with a favourable safety profile that can delay the need for irreversible surgery. In addition, it is important to note that colectomy rates were comparable to those seen in anti-TNFs trials with stricter selection criteria. This shows that Adacolumn^® may be an alternative to elective surgery when compared to anti-TNFs in a less-selected population.

Ultimately, these data show that Adacolumn^® provided clinical benefit in a large cohort of steroid-dependent patients with ulcerative colitis with previous failure to biologics.

The ART study was a single arm, open-label, multicentre trial conducted at 18 centres across the UK, France and Germany among 95 non-preselected patients who were 18–75 years old with moderate-to-severe, steroid-dependent active UC with insufficient response or intolerance to biologics. Patients received 5 to 8 weekly apheresis sessions with Adacolumn^®. The primary endpoint was clinical remission rate (Clinical Activity Index ≤4) at week 12. Main secondary efficacy endpoints included clinical response (reduction in CAI of ≥ 3), steroid-free remission, and colectomy rates. Patients were followed-up until week 48 and retrospectively for colectomy events at week 96.

Luisa Avedano, CEO, European Federation of Crohn’s and Ulcerative Colitis Associations (EFCCA), said:

Ulcerative colitis affects millions of people across Europe, particularly young people. The disease can be extremely debilitating which can seriously affect a patient’s quality of life and limit their life opportunities. Currently there is no cure, with many patients either facing irreversible surgery or treatments with adverse side effects. It is therefore so important that patients have additional treatment options, such as Granulocyte Monocyte Apheresis, that are not only effective but can also help improve their outcomes and quality of life.

Results from the study also showed that in weeks 24 and 48, remission rates were 34% and 33% respectively and response rates were 44.7% and 39.4%, respectively. Out of 30 patients with prior failure of immunosuppressants and anti-TNFs, 30%, 33.3% and 20% were in remission in weeks 12, 24 and 48 respectively. Steroid-free remission in weeks 12, 24 and 48 was achieved by 19.2%, 19.2% and 18.1% respectively. Sustained remission or response was observed in 27.7% of patients at 48 weeks.

Ole Vahlgren, CEO & President of Otsuka Pharmaceutical Europe Ltd., said:

There is an urgent need for treatments in ulcerative colitis patients who have run out of options. Otsuka are committed to improving the lives of people in Europe and across the globe with ulcerative colitis, particularly in this hard-to-treat population.

The ART data represents an important finding in the treatment and management of ulcerative colitis in this group of patients since not only has it shown clinical benefit but also a favourable safety profile.

The ART study is being presented at DDW in San Diego, California, on 23 May 09:30-16:00 (PDT).

Adacolumn^® is not FDA approved for marketing or investigational use in the United States. Adacolumn^® is approved for use in the EU (CE marked) and in Japan since 2001.