Alimentary TractLong-term oral plus topical mesalazine in frequently relapsing ulcerative colitis
Introduction
Mesalazine is the most commonly used drug in ulcerative colitis (UC), first as an active moiety of Salazopyrine, then as a single molecule contained in slow or controlled release capsules [1], [2]. In spite of the continuous use of the drug over the last 50 years, the therapeutic range of mesalazine remains to be clearly established and thus, its optimal dosage and route of administration are still debated [3], [4], [5].
A cross-sectional study has demonstrated that the anti-inflammatory effect of mesalazine is closely related to its mucosal concentration [6]. In other words, in a given colonic segment, the higher the mucosal concentration of mesalazine, the better the endoscopic and histological conditions of the mucosa. It is, therefore, reasonable to hypothesise that the optimal dose should be the one ensuring an adequate mucosal drug concentration in the affected sites [7]. However, mesalazine has a topical effect, which means that the drug may significantly concentrate into the intestinal mucosa only during its absorptive process. Thus, if it is absorbed by inflamed mucosa it may concentrate in the inflamed tissue, but if the drug is absorbed by normal mucosa it is almost completely lost for its therapeutic use. Thus, the goal of treatment is not only to achieve an optimal dosage, but especially to take the drug where it needs [8].
Pharmacokinetic studies have demonstrated that, when given per os, the active moiety of mesalazine is delivered mainly to the distal ileum and proximal large bowel thus ensuring a higher mucosal drug concentration in the right than in the left colon, with only negligible amounts of the drug reaching the rectal mucosa [9], [10]. The increase in the oral dosage further increases the mucosal concentration in the proximal colonic segments, but does not significantly modify distal drug distribution [11]. Conversely, topical mesalazine administration assures a considerable drug availability in the recto-sigmoid sites and, to a lower extent, also in the descending colon [12], [13]. Therefore, it appears that, if we would increase mucosal mesalazine concentration in UC patients along the entire length of their large bowel, beside an increase of oral dosage, a continuous topical treatment should be given.
On the basis of these pharmacokinetic considerations, the present longitudinal study was aimed to verify whether an increasing of oral dosage of mesalazine, associated with its continuous topical administration, could increase mucosal drug concentration and modify the clinical course of a particular group of UC patients at high risk of relapse, with a not mild disease, that actually need repeated hospitalisations, courses of steroids and/or immunosuppressive drugs [14], [15].
Section snippets
Patients and methods
This study was designed to compare the clinical course of UC patients recorded during the 2 years prior to the study (referred period RP) with that seen in the subsequent 2 years, when the same patients were assigned to the treatment under investigation (study period SP). This was a “before-after” comparison study in which each patient was compared with him/herself, thus representing his/her own control.
The clinical, endoscopic and histological characteristics of all consecutive UC patients
Results
During SP no severe or moderate recurrences were recorded and only six patients showed mild signs of relapse. A total number of 80 episodes of relapses were observed during RP and 8 during the SP (p < 0.0001). Mild relapses were 25 during RP and 8 during SP (p < 0.0001), moderate relapses were 36 during RP and none during SP (p < 0.0001) and severe relapses occurred in 19 instances during RP but in none during SP (p < 0.0001) (Table 2). All relapses occurred when the frequency of topical treatment was
Discussion
Previous cross-sectional studies have demonstrated that the efficacy of mesalazine is related to its mucosal concentration and that to increase large bowel drug availability, the oral dosage should be increased and a topical treatment should be continuously associated [6], [13], [20]. In the present investigation, we adopted this therapeutic strategy in a longitudinal study to establish whether or not it could change the clinical course of a particular group of UC patients with a moderate to
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Cited by (57)
Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on topical therapy in ulcerative colitis
2020, Gastroenterologia y HepatologiaSecond European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 2: Current management (Spanish version)
2015, Revista de Gastroenterologia de MexicoNanotechnology in the treatment of inflammatory bowel diseases
2014, Journal of Crohn's and ColitisCitation Excerpt :5-ASA, on the other hand, has been in use from more than 70 years, with proven efficacy and only modest long-term side effects, with limitations however, regarding its topic action and complex therapeutic protocol.5–10 In fact, in UC and in prevention of recurrence in CD, the major problem is to maintain an adequate concentration of the drug in the inflamed mucosa in order to obtain a reduction of recurrences and reduce the need of steroids and hospitalization.11–15 These results, sometimes may require multiple daily administrations of large numbers of pills — together with enemas, suppositories or foam, a practice that has the effect of reducing a full adherence to treatment in about half of patients with a fivefold increased risk of recurrence.16,17
Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 2: Current management
2012, Journal of Crohn's and ColitisCitation Excerpt :Further support for the use of combined oral and rectal mesalazine therapy in patients with left sided colitis comes from an extrapolation of a trial of combination therapy for extensive colitis.21 Furthermore, there is evidence that topical therapy achieves higher rectal mucosal 5ASA concentrations than oral therapy22 and is associated with improved clinical outcome.22,23 Mesalazine foam enemas are not inferior to liquid enemas for inducing remission,24 so either are appropriate treatments for left-sided colitis.
Inflammatory Bowel Disease
2012, Colorectal Surgery