ORLANDO – In a case of nothing being better than something, mesalamine granules proved to be less effective than placebo at preventing the recurrence of diverticulitis, an investigator reported at the annual Digestive Disease Week.
Among 333 patients with diverticulitis in an intention-to-treat population, 67.9% of patients randomly assigned to mesalamine granules (Salofalk) had 48 relapse-free weeks of follow-up, compared with 74.4% of patients assigned to placebo. This difference was not significant, but in a per-protocol population, placebo was significantly better (P = .018), said lead investigator Dr. Wolfgang Kruis from the University of Cologne, Germany.
Dr. Wolfgang Kruis
The trial was stopped early after an interim analysis showed no benefit for mesalamine.
"The results of this trial do not support the use of mesalamine for the maintenance of relapse-free diverticular disease," Dr. Kruis said.
Mesalamine, whose chemical name is 5-aminosalicylic acid (5-ASA), appeared to have no effect on biomarkers of inflammation, but the therapy was safe and was not associated with unexpected adverse events, he noted.
Mesalamine and other 5-ASA drugs are commonly prescribed to treat ulcerative colitis, and previous open-label studies have shown clinical benefit of these agents in patients with recurrent diverticulitis, Dr. Kruis said.
To see whether those findings would stand up to a more rigorous randomized, double-blind, controlled trial, he and his colleagues from 57 centers in 11 countries compared mesalamine granules delivered 3 g by mouth daily to placebo in 333 patients (165 assigned to mesalamine and 168 to placebo) for whom complete information was available (the full-analysis population). A total of 270 patients completed the 48 weeks of therapy, 133 of whom were assigned to mesalamine and 137 to placebo (the per-protocol population).
As noted before, numerically but not significantly more patients on placebo in the full-analysis population were recurrence free at 48 weeks, where recurrence was defined as a C-reactive protein (CRP) level above the upper limit of normal, or leukocytosis plus the presence of diverticulitis-like clinical signs plus typical findings on CT scans or ultrasound.
But in the per-protocol analysis, 78.9% of patients on the 5-ASA agent had no recurrent diverticulitis after 48 weeks, compared with 89.8% of placebo-treated controls (P = .018).
There was no significant difference in mean time in days to recurrence, mean erythrocyte sedimentation rate, mean CRP levels, or mean leukocytosis throughout the study.
"It really was remarkable that [patients on mesalamine] did worse," commented Dr. Nicholas J. Talley from the Mayo Clinic in Rochester, Minn., who was not involved in the study.
In an interview, Dr. Talley speculated that the difference seen in the per-protocol analysis suggests that "perhaps suppressing inflammation in this setting actually sets up a different cascade for some reason that makes people worse."
Dr. Talley noted that the authors did not perform baseline colonic biopsies, and it is possible that there was some undetected heterogeneity in the population that might explain the lack of a benefit from the active drug.
"Diverticular disease and diverticulitis are probably not one entity," he said.
The study was funded by Dr. Falk Pharma. Dr. Kruis disclosed receiving speaking and teaching fees from the company, and three of his coauthors are company employees.