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

Abstract

Objectives5-aminosalicylate (mesalazine; 5-ASA) is an established first-line treatment for mild-to-moderate ulcerative colitis (UC). This study aimed to model the benefits of optimising 5-ASA therapy.MethodsA decision tree model followed 10 000 newly diagnosed patients with mild-to-moderately active UC through induction and 1 year of maintenance treatment. Optimised treatment (maximising dose of 5-ASA and use of combined oral and rectal therapy before treatment escalation) was compared with standard treatment (standard doses of 5-ASA without optimisation). Modelled data were derived from published meta-analyses. The primary outcomes were patient numbers achieving and maintaining remission, with an analysis of treatment costs for each strategy conducted as a secondary outcome (using UK reference costs).ResultsDuring induction, there was a 39% increase in patients achieving remission through the optimised pathway without requiring systemic steroids and/or biologics (6565 vs 4725 for standard). Potential steroidal/biological adverse events avoided included: seven venous thromboembolisms and eight serious infections. Out of the 6565 patients entering maintenance following successful induction on 5-ASA, there was a 21% reduction in relapses when optimised (1830 vs 2311 for standard). This translated into 297 patients avoiding further systemic steroids and 214 biologics. Optimisation led to an average net saving of £272 per patient entering the model for the induction and maintenance of remission over 1 year.ConclusionModelling suggests that optimising 5-ASA therapy (both the inclusion of rectal 5-ASA into a combined oral and rectal regimen and maximisation of 5-ASA dose) has clinical and cost benefits that supports wider adoption in clinical practice.

Non‐invasive monitoring and treat‐to‐target approach are cost‐effective in patients with mild–moderate ulcerative colitis

“…However, the most cost‐effective strategy was the one based only on symptoms. Recently, another cost‐effectiveness evaluation on dose optimisation strategies in both induction and maintenance of remission in patients with mild‐to‐moderately active UC using a 1‐year time horizon was published 25 . In this study, the FC assessment was included only to identify the patients who need escalation of 5‐ASA dose, and not as a biomarker to guide the decision‐making process further in the treatment algorithm.…”

“…with mild-to-moderately active UC using a 1-year time horizon was published. 25 In this study, the FC assessment was included only to identify the patients who need escalation of 5-ASA dose, and not as a biomarker to guide the decision-making process further in the treatment algorithm.…”

Inflammatory Bowel Disease Treatments and Predictive Biomarkers of Therapeutic Response

“…These therapies are small molecules that are administered orally or rectally to decrease the inner wall inflammation of the intestines (Figure 2). Aminosalicylates are known to be the first-line treatment option for UC patients with mild-to-moderate disease and the second most prescribed IBD medicine [40][41][42] (Figure 2a and b). Aminosalicylates have a wide range of anti-inflammatory and immunomodulatory functions, including inhibition of cyclooxygenase, lipoxygenase, platelets-activating factor, interleukin (IL)-1 nuclear factor B, and scavenging of reactive oxygen species [43][44][45].…”

Significance of 5-Aminosalicylic Acid Intolerance in the Clinical Management of Ulcerative Colitis

“…One study showed that the local concentration of 5-ASA and its acetylated form, N-acetyl-5-ASA, in the sigmoid colon was significantly correlated with endoscopic remission in patients with UC regardless of the formulation of 5-ASA used [ 12 ], suggesting the importance of optimizing the local concentration of 5-ASA. Indeed, a subsequent study showed that optimization of 5-ASA therapy by maximizing the oral dose and/or combining oral and topical formulations of 5-ASA had clinically beneficial effects in terms of reducing the dose of systemic corticosteroids and the need for advanced therapies [ 13 ]. Therefore, optimization of 5-ASA therapy is considered beneficial in terms of both patient outcomes and health care costs in the treatment of UC by minimizing unnecessary introduction of various molecular targeted immunosuppressive agents and the adverse events associated with their use.…”

“…There is no significant difference in the long-term risk of flares between patients with a low or high average daily dose of 5-ASA [20], suggesting that the requirement of high-dose 5-ASA may need to be stratified by disease behavior, biomarkers, and endoscopic findings. Indeed, optimization of 5-ASA results in better clinical outcomes [13]. It is important to improve adherence by selecting the appropriate drugs for individual patients and optimizing the dose and preparation of 5-ASA according to disease activity.…”