Efficacy of Oral, Topical, or Combined Oral and Topical 5-Aminosalicylates, in Ulcerative Colitis: Systematic Review and Network Meta-analysis

Abstract

Background 5-Aminosalicylates [5-ASAs] are the mainstay of treatment for ulcerative colitis [UC]. The optimum preparation, dose, and route of administration for UC remain unclear. We conducted a network meta-analysis to examine this issue. Methods We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to December 2020. We included randomised controlled trials [RCTs] comparing oral, topical, or combined oral and topical 5-ASAs, with each other or placebo for induction of remission or prevention of relapse of UC. Results were reported as pooled relative risks [RRs] with 95% confidence intervals [CIs] to summarise effect of each comparison tested, with treatments ranked according to P-score. Results We identified 40 RCTs for induction of remission and 23 for prevention of relapse. Topical mesalazine [P-score 0.99], or oral and topical mesalazine combined [P-score 0.87] ranked first and second for clinical and endoscopic remission combined. Combined therapy ranked first in trials where ≥50% of patients had left-sided/extensive disease, and topical mesalazine first in trials where ≥50% of patients had proctitis/proctosigmoiditis. High-dose [≥3.3 g/day] oral mesalazine ranked third in most analyses, with the most trials and most patients. For relapse of disease activity, combined therapy and high-dose oral mesalazine ranked first and second, with topical mesalazine third. 5-ASAs were safe and well tolerated, regardless of regimen. Conclusions Our results support previous evidence; however, higher doses of oral mesalazine had more evidence for induction of remission than combined therapy and were significantly more efficacious than lower doses. Future RCTs should better establish the role of combined therapy for induction of remission, as well as optimal doses of oral 5-ASAs to prevent relapse.

Modelling the benefits of an optimised treatment strategy for 5-ASA in mild-to-moderate ulcerative colitis

“…A further limitation is in the data available to use for construction of this model and the variation in definitions that have been used in trials of therapies in UC. [11][12][13] This limited the definition of remission used in this model to clinical remission in the base case, when a definition of combined clinical and endoscopic remission would have been preferred as a more robust and clinically relevant definition. However, this is an issue that has been strongly influenced by the evolution in thinking and treatment aims over the years and is, therefore, applicable to any study aiming to pool data on the efficacy of 5-ASA.…”

“… 12 25 If no Cochrane review was available for a treatment, recent systematic literature reviews and meta-analyses were identified. 11 14 26 The non-Cochrane studies used provided sufficient detail on dosing to allow for the required dosing options in this model, and the reporting of clinical and/or endoscopic remission/relapse measures. If multiple studies fulfilled these criteria, the most recent and appropriate study was chosen to maximise the clinical data considered.…”

“…10 A number of studies have shown that these approaches can increase the effectiveness of 5-ASA therapy. [11][12][13] A further step in 5-ASA optimisation has been the use of once daily dosing, which has demonstrated equivalent efficacy to divided dosing regimens and can improve patient adherence to treatment. 12 13 When moving beyond 5-ASA, further steps can be taken to optimise corticosteroid therapy by reducing systemic steroid exposure in order to minimise the incidence of AEs.…”

Efficacy and safety of oral Pentasa (prolonged-release mesalazine) in mild-to-moderate ulcerative colitis: a systematic review and meta-analysis

“…Recent meta-analyses of 5-ASAs in UC have focused on them more as a class, in particular, explored dosing regimens, and did not assess the mesalazines individually against placebo [16][17][18] . Pentasa has been available for over 30 years with an on-going clinical development program throughout that time.…”

Hospitalisation for Drug Infusion Did Not Increase Levels of Anxiety and the Risk of Disease Relapse in Patients with Inflammatory Bowel Disease during COVID-19 Outbreak

“…When standard treatments fail to achieve remission [10], patients with IBD are treated with biologic drugs, which have been associated with a reduction in immune response in case of infections. In particular, the use of anti-TNF drugs has been associated with an increased risk of viral and bacterial infections, including pneumonia [11][12][13].…”