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Corticosteroids are the principal therapy for patients hospitalized with acute severe ulcerative colitis (UC). Whether the addition or continuation of mesalamine with corticosteroids during hospitalization is superior to corticosteroids alone has not been clear, although many patients are on existing mesalamine therapy at admission. This clinical dilemma is pressing for patients with acute severe UC, since life-threatening deterioration and possible colectomy are at stake.

To further our understanding of mesalamine's benefit in this setting, Shomron Ben-Horin, MD, of Sheba Medical Center at Tel-Aviv University in Israel, and colleagues in the ComboMesa study group conducted an investigator-blinded randomized controlled trial in seven countries.

Ben-Horin spoke about the study, recently published in , in an interview with the Reading Room.

Do hospitalists commonly give mesalamine to patients with acute UC? And what is the clinical downside of adding this?

Ben-Horin: In our previous of more than 300 experts in 14 countries, including the U.S., we found that more than 60% of respondents routinely gave mesalamine to patients with acute UC receiving steroids. The clinical downside of this is additional cost, additional pill burden for severely ill patients, and the small potential for side effects, although this risk is admittedly low with mesalamine.

Did your group have a working hypothesis as to the findings that would emerge from the trial?

Ben-Horin: The working hypothesis assumed there would be a small advantage in efficacy with the combination of corticosteroids and mesalamine over corticosteroids alone.

What was the composition of the study cohort?

Ben-Horin: The study comprised 147 UC patients admitted to hospitals in 10 centers in seven countries with severe UC requiring intravenous corticosteroids. All had a score of >10, indicating active disease with no response to therapy. Importantly, patients admitted while receiving biologics were excluded. Patients were randomized to receive corticosteroids alone or corticosteroids plus mesalamine.

What was the main study outcome and how will it impact treatment going forward?

Ben-Horin: The main outcome was that contrary to our hypothesis and to the common practice of gastroenterologists revealed by our global survey, mesalamine conferred no additional benefit when administered with corticosteroids compared with corticosteroids alone.

Treatment success by day 7, need for salvage therapy with cyclosporine/infliximab or surgery, and duration of hospitalization were all comparable between the two groups. Thus, the inevitable conclusion is that there is no role for mesalamine during the first 7 days of hospitalization for patients with acute UC receiving corticosteroids.

Were you surprised by any of the findings -- were there any unexpected results?

Ben-Horin: An exploratory post-hoc analysis yielded a surprising finding: patients who took mesalamine with corticosteroids during the 7 days' hospitalization and for 3 months subsequently were less likely to require initiation of biologics upon cessation of corticosteroids. This was especially true for patients who had not received mesalamine before hospitalization, but it is notable that this finding had borderline statistical significance, so should be interpreted with caution.

Were there any major study limitations?

Ben-Horin: The study did not include patients treated with biologics, so the findings need to be corroborated for this population.

What's the next research step or question that needs to be addressed?

Ben-Horin: In general, I am a strong believer in the need to explore strategies combining different drugs with different modes of action in order to try to surpass the therapeutic ceiling of current therapies. Preferably, we should examine combining agents in an affordable manner that will make these regimens, if proved effective, widely accessible to patients.

Continuing or starting mesalamine with corticosteroids to better maintain remission over time and to reduce the need for costly biologics needs to be explored further.

In a previous we found the simple combination of 95% curcumin with mesalamine in patients with mild to moderate UC enabled better remission and obviated the need to escalate therapy in a non-negligible portion of patients.

such as induction with cyclosporine followed by a biologic such as vedolizumab (Entyvio) is another emerging concept requiring further study. Strategies combining already-used compounds are worth exploring for the benefit of UC patients.

You can read the abstract of the study here, and about the clinical implications of the study here.