Mesalamine for Inflammatory Bowel Disease: Recent Reappraisals

Abstract

Derived from the historical molecule sulfasalazine, mesalamine has remained one of the mainstays for treatment of inflammatory bowel disease in the last 50 years. Recent advancement in both clinical and basic research has led to reappraise the drug under two crucial aspects. Firstly, there has been a re-evaluation of the chemo-protective effect of mesalamine against sporadic colorectal cancer. Evidence that inflammation plays a strong role in tumor induction from one side, and demonstration that mesalamine can touch on specific molecular steps enhancing apoptosis on the other side have re-shaped the indications of mesalamine for ulcerative colitis. Secondly, the role of thiopurines (azathioprine and 6-MP) in the maintenance of remission of ulcerative colitis has been reiterated by the results of several clinical trials. During attempts at clarifying the reasons why certain patients appear to be resistant to thiopurines, it was interestingly found that mesalamine can interfere thiopurine metabolism, causing an increased blood concentration of the specific immunosuppressive metabolites and a sequential enhancement of drug effectiveness. Mesalamine is therefore being studied as a means to overcome the genetically determined resistance to thiopurines. Such sharpened indications have reiterated attention to correct dosing: the results of controlled trials have shown mesalamine to be fully effective at twice the traditional daily dosage (4.8 grams instead of 2.4). The attendant problems of compliance seem to find solution in the availability of multi-matrix system formulations. This mesalamine story reminds us that in the absence of an etiological target capable to guide research to trace one abrogating molecule, (as it has happened for viral hepatitides for example), treatment of inflammatory bowel disease remains anti-inflammatory in nature and thus multifaceted. Besides justified use of cutting-edge technology to find novel molecules, smart re-evaluation of what is already in our hands can sometimes bring about unexpected breakthroughs.

Metabolomic Applications to Decipher Gut Microbial Metabolic Influence in Health and Disease

“…Advancing knowledge regarding the mechanisms of IBD has led to the development of different therapeutic solutions based on surgery (Harper et al, 1983; Korelitz et al, 1985), cannabinoids (Duncan et al, 2005), immunosuppression (Remicade, Mesalamine, etc. ; Siemanowski and Regueiro, 2007; Actis et al, 2008), and alternatively probiotic supplementation (Reid et al, 2003). However, the IBD diagnosis is only possible at an advanced disease state when symptoms are detectable by radiology, endoscopy with biopsy of pathological lesions (Ahmadi and Polyak, 2007).…”

Pediatric Crohn's disease: epidemiology and emerging treatment options

“…47 Effective adult doses range from 4-6 gm per day (40-75 mg/kg/day in children). 48 The sulfapyridine component of sulfasalazine has been implicated in many of its side effects, including allergic reactions, 49,50 and efforts have been directed toward producing an effective 5-ASAbased drug which lacks sulfapyridine and is formulated in such a manner as to maximize delivery to the inflamed tissue -either colon or terminal ileum.…”

“…Side effects of sulfasalazine include fever, rash, hemolytic anemia, hepatitis, pancreatitis, headache, nausea, malaise, and anorexia. 49,50 Newer ASA preparations are generally considered safer than sulfasalazine, but nevertheless are associated with adverse effects. Mesalamine has been reported to cause diarrhea, nephrotoxicity at an average rate of 0.26% per patient year and pancreatitis seven times more frequently than sulfasalazine.…”

“…Mesalamine has been reported to cause diarrhea, nephrotoxicity at an average rate of 0.26% per patient year and pancreatitis seven times more frequently than sulfasalazine. 49,58,59 It can also rarely but dramatically affect the lungs, most likely through an allergic reaction, causing eosinophilic pneumonia, bronchiolitis obliterans, pleural effusion, or pulmonary fibrosis. 42,50,59,60 Mesalamine has been reported to be safe and effective in children and adolescents in the limited data that is available.…”

A cost-effectiveness analysis of MMX mesalazine compared with mesalazine in the treatment of mild-to-moderate ulcerative colitis from a UK perspective

“…The chronic symptomatic morbidity is associated with impairment of healthrelated quality of life, higher unemployment and productivity loss 2 . Oral mesalazine preparations are a re-emerging treatment option in mild-to-moderate UC and were developed with the primary intent of delivering maximal amounts of mesalazine to the colonic tissue 3 . A new mesalazine, (Mezavant XL*) has been developed utilising MMX technology (trademark of Cosmo Technologies Ltd, Wicklow, Ireland) and is indicated for the induction of clinical and endoscopic remission in patients with mild-to-moderate, active UC and for the Patients suffer mortality either from all-cause mortality or surgery *In the base case all patients are considered to be fully adherent when in remission.…”