Combo Treatment Disappoints in Acute Severe Ulcerative Colitis

Hospitalized patients with acute severe ulcerative colitis (ASUC) did not benefit from add-on aminosalicylic acid (5-ASA) to corticosteroids (CS), according to results from the ComboMesa Collaborative Trial.

In an intention-to-treat analysis involving 149 patients with ASUC, no significant difference was seen between the number of patients who responded to treatment by 7 days using maximal mesalamine therapy plus corticosteroids versus corticosteroids alone (72.6% vs 76.3%, OR 0.82, 95%CI 0.39-1.72, P=0.60), reported Shomron Ben-Horin, MD, of the Sheba Medical Center in Tel Aviv.

Additionally, no significant difference was also observed for length of stay, 90-day colectomy, or C-reactive protein (CRP) normalization rates among groups, he said at the virtual Crohn's & Colitis Congress.

"Because outcomes of CS plus 5-ASA were comparable to CS alone, there is no need to add or continue mesalamine during hospitalization in ASUC patients receiving IV corticosteroids," Ben-Horin told MedPage Today.

"It has been disappointing that we as the IBD [inflammatory bowel disease] community do not have any data on whether continuing or starting 5-ASA with CS in these patients offer any benefit over CS alone or will 5ASA merely increase costs, pill burden, and potential additional side effects during hospitalization," he explained.

But the results confirm what the majority of IBD specialists likely suspected -- that the addition of 5-ASA will not impact important outcomes in terms of response to corticosteroids, CRP levels, or length of hospitalization, commented Russell Cohen, MD, of the University of Chicago Medicine, who was not involved in the study.

"These results are helpful in simplifying patient treatment regimens and decreasing medication costs associated with the multiple daily pill 5-ASA regimens," he stated.

Ben-Horin explained that "Patients with acute severe colitis are challenging, and are at imminent risk of failing medical therapy and colectomy. Optimizing their therapy by any means is crucial."

IV corticosteroids are the mainstay treatment for ASUC. A 2016 study found that mesalamine therapy offered long-term maintenance of UC remission in patients with a history of prior corticosteroid therapy for UC flares or maintenance of UC remission. In a previous survey-based study, Ben-Horin's group found that most clinicians (65% of 330) in 12 countries continued to use 5-ASA, while 35% discontinued 5-ASA, for hospitalized patients with ASUC.

"Although 5ASA are generally considered safe, they are occasionally associated with severe adverse events [AEs]," they noted.

For the current study, the authors enrolled hospitalized patients with ASUC, and randomized them to receive IV corticosteroids plus oral mesalamine (4 grams per day) and topical mesalamine (1 g per day; n=73) or IV corticosteroid monotherapy (n=76). Patients across seven countries and at 10 centers were stratified by 5-ASA use at admission.

Study participants had a confirmed UC diagnosis, and were hospitalized with exacerbated ASUC, but did not receive oral systemic corticosteroids for over 14 days before hospitalization. Patients taking a stable dose of thiopurine for 2 months prior to enrollment were included. However, patients treated with a biologic, cyclosporine, or tacrolimus within the prior 3 months were excluded.

The primary outcome assessed the percentage of patients who responded to the treatment by day 7 in the two arms, while secondary outcomes assessed colectomy rates, the need for rescue medications (cyclosporine/infliximab [Remicade]) during hospitalization, length of stay, and normalized CRP levels by 7 days.

A reduction in over 3 Lichtiger score points, with an absolute score below 10 for 2 prior consecutive days not requiring rescue medication or surgery, defined treatment response.

Less than half of participants in both study groups were women (47%-49%), with a median age of about 41, and a median BMI of around 23. The median disease duration was 4 years. Both groups had an average Lichtiger score of 13.

More patients in the single-agent group were on oral steroids at admission versus the combination group (21% vs 7%). Also, 74% of the latter were on oral 5-ASA at admission versus 70% of the former.

The authors reported that two patients in the combination group, and four in the single-agent group, experienced AEs, such as infections and superficial vein thrombosis. One patient in the combination group had treatment-related pancreatitis, according to Ben-Horin's group, which resolved once mesalamine was stopped (patient continued on prednisone). There were no deaths during the trial.

Exploratory analysis found a reduced need for biologics among those who received corticosteroids with 5-ASA by 30 (P=0.11) and 90 days (P=0.07), but Ben-Horin cautioned that this "interesting signal" needed further study.

Study limitations included the fact that it was investigator-blinded trial. Also, the analysis may have been underpowered to identify superiority of the combination treatment "given the 70-90% effect-size margins in the power analysis," according to the authors. Finally, post-interventional endoscopies were not available to support assessments, although they pointed out that "proving endoscopic response is not generally endorsed in the ASUC clinical trials' setting."

A related earlier study found that biologic-experienced patients hospitalized with ASUC who were given off-label, high-intensity doses of tofacitinib (Xeljanz) plus IV corticosteroids seemed to have a reduced chance of undergoing colectomy.

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