No benefit to adding 5-ASAs to steroids in acute severe UC

The addition of 5-aminosalicylic acid (5-ASA) to standard corticosteroid treatment did not improve outcomes in patients hospitalized with acute severe ulcerative colitis (UC), according to a study presented at the Crohn’s and Colitis Congress 2022.

The trial, conducted in 10 centres in seven countries, included 149 adults (median age 41 years, 70 female) hospitalized with acute severe UC (Lichtiger score ≥10). They were randomized to receive corticosteroids (~60 mg/day of methylprednisolone) either alone or in addition to 5-ASA (4 g/day of oral mesalamine plus topical mesalamine 1 g/day as tolerated). Patients should not have been on oral corticosteroids for >14 days before hospitalization and those who were on thiopurine pre-study needed to be on a stable dose 2 months before the study began. Patients with exposure to biologics, cyclosporine, or tacrolimus in the prior 3 months were excluded.

Baseline characteristics were generally comparable between groups, though more patients in the corticosteroids-alone compared with corticosteroids plus 5-ASA arm were on oral steroids at admission (21.1 percent vs 6.8 percent).

The proportion of patients with treatment response by day 7 (reduction in >3 points in the Lichtiger score and absolute score <10 without the need for rescue medications* or colectomy) did not significantly differ between those who received corticosteroids plus 5-ASA compared with those who received corticosteroids alone (72.6 percent vs 76.3 percent; odds ratio, 0.82, 95 percent confidence interval, 0.39–1.72; p=0.60). [Crohn’s and Colitis Congress 2022, session 55; Inflamm Bowel Dis 2022;28 Suppl 1:S14]

The need for rescue medications was similar between groups (p=0.9). Duration of hospitalization also did not differ between patients who received corticosteroids plus 5-ASA compared with those who received corticosteroids alone (p=0.8), nor did normalization of elevated C-reactive protein levels at day 7 (p=1). Colectomy rate at day 90 was comparable between groups.

However, post hoc analysis showed a trend toward a reduced requirement for biologic therapy among patients who received corticosteroids plus 5-ASA compared with those who received corticosteroids alone at day 30 (p=0.11) and day 90 (p=0.07).

This finding requires further evaluation, pointed out study author Professor Shomron Ben-Horin from the Sheba Medical Center and Tel-Aviv University, Tel Aviv, Israel.

Logistic regression analysis did not reveal any specific baseline factors associated with the primary outcome including prednisone use pre-admission, 5-ASA or thiopurine use at admission, extensive colitis, fever (>37.8°C), or Lichtiger score.

Six and four patients in the corticosteroids plus 5-ASA and corticosteroids-alone groups, respectively, experienced adverse events (AEs; p=0.68). Four of the AEs were infections. One patient in the corticosteroids plus 5-ASA group experienced pancreatitis 19 days after first exposure to mesalamine which resolved after discontinuation of mesalamine with continued prednisone. There were no deaths during the trial.

Despite the general safety of 5-ASA, severe AEs can occur as shown in the patient with 5-ASA-induced pancreatitis, said Ben-Horin.

“Intravenous corticosteroids are the mainstay of treatment in hospitalized acute severe UC,” he said.

“5-ASAs are well-established agents for the treatment of mild-to-moderate UC,” he continued. However, data on the potential benefit of continuing or adding 5-ASAs to systemic corticosteroid therapy in patients with acute severe UC are lacking.

“This … trial is the first to examine this clinical dilemma and shows no benefit [with the addition] of 5-ASA [to corticosteroids] in hospitalized acute severe UC patients. This was true for all outcomes sought including clinical response, need for salvage therapy, duration of hospitalization, and biomarker normalization.”

“It may be hard to justify the associated costs and pill-burden of adding [5-ASAs], even for a short period of hospitalization, given their apparent lack of benefit in this clinical setting. [This finding] should inform inflammatory bowel disease experts and hospitalists managing these challenging patients to stop unnecessary 5-ASAs during hospitalization,” he concluded.