5-ASA colonic mucosal concentrations resulting from different pharmaceutical formulations in ulcerative colitis

Abstract

IBD patients showed significant variability in mucosal 5-ASA concentrations depending on the type of formulation, and the highest mean concentration was achieved using pH-dependent-release formulations.

Does the 5-Aminosalicylate Concentration Correlate with the Efficacy of Oral 5-Aminosalicylate and Predict Response in Patients with Inflammatory Bowel Disease? A Systematic Review

“…Our finding that an increase in mucosal concentration is associated with quiescent disease is in line with studies that compare oral versus oral plus topical (combination) 5-ASA therapy. Placebo controlled trials showed that combination therapy is more effective than oral therapy alone [59], and pharmacokinetic studies established higher mucosal concentrations during combination therapy than during oral therapy alone [33,45,46,60,61]. Frieri et al [33] analysed both mucosal concentrations and therapeutic efficacy in UC patients using oral therapy versus combination therapy.…”

“…Strikingly, several individual studies reported lower mucosal 5-ASA concentrations during inflammation. D'Inca et al [44] found a significant lower mucosal 5-ASA concentration during the active state of UC, both based on endoscopic and histological criteria, compared to quiescent UC (endoscopic active state 35.7 ± 5.7 ng/mg vs. remission 60.1 ± 8.0 ng/mg, p = 0.02, and histologic active state 35.5 ± 5.6 ng/mg vs. remission 67.5 ± 9.2 ng/mg, p < 0.001) [45]. Naganuma et al [46] detected an inverse correlation between the disease activity index of UC patients and mucosal van 5-ASA concentrations (r = 0.71, p < 0.001).…”

“…In this study, mucosal 5-ASA cut-off levels were defined for the risk of recurrence in CD patients in whom an ileocecal resection had been performed: 80% recurrence rate at a colonic mucosal 5-ASA concentration < 20 ng/mg, 6% recurrence rate at a colonic mucosal 5-ASA concentration between 29 and 100 ng/mg and 0% recurrence rate at a colonic mucosal 5-ASA concentration higher than 100 ng/mg [48]. To put this into perspective, 28% of Asacol users showed a mucosal 5-ASA concentration of 70 ng/mg or higher [45]. Figure 2 shows a subgroup analysis of 4 studies which scored "+" for domain in our critical appraisal relevance criteria, that is, studies that compared patients with active UC to quiescent UC [44][45][46][47].…”

“…To put this into perspective, 28% of Asacol users showed a mucosal 5-ASA concentration of 70 ng/mg or higher [45]. Figure 2 shows a subgroup analysis of 4 studies which scored "+" for domain in our critical appraisal relevance criteria, that is, studies that compared patients with active UC to quiescent UC [44][45][46][47]. Patients receiving 2-3 g/day of either Asacol, Pentasa or Sulfasalazine had higher mucosal 5-ASA concentrations during remission in each study.…”

“…A limited number of studies identified significant different mucosal 5-ASA values when using different formulations. D'Inca et al [45] found higher mucosal 5-ASA concentrations using Asacol compared to Sulfasalazine and Pentasa and De Vos et al [50] found lower mucosal 5-ASA concentrations after using azo-bonded prodrugs instead of time-and pH dependent release mesalazine compounds. Conversely, 2 other studies found higher mucosal concentrations of 5-ASA using the azo bonded pro-drug formula Olsalazine or Sulfasalazine as compared to Pentasa or Salofalk [46,51].…”