Is your patient taking the medicine? A simple assay to measure compliance with 5‐aminosalicylic acid‐containing compounds

Abstract

Summary Background : Poor compliance with 5‐aminosalicylic acid therapy has been reported amongst patients with inflammatory bowel disease. Currently, there is no easy method to monitor 5‐aminosalicylic acid; however, the chemical similarity between 5‐aminosalicylic acid and salicylate might provide a solution. Aim : To determine the feasibility of using salicylate levels to monitor compliance with 5‐aminosalicylic acid medication. Methods : Thirty‐six patients with inflammatory bowel disease, taking maintenance 5‐aminosalicylic acid, provided either a paired serum and urine sample or an intestinal biopsy. Samples were split into two: half were sent to the hospital biochemistry department for salicylate measurement, and half were analysed for 5‐aminosalicylic acid and its metabolite, N‐acetyl‐5‐aminosalicylic acid, using high performance liquid chromatography. Correlation between the results was calculated. Results : Serum and urine were available for 25 patients. Serum salicylate was undetectable, but urinary salicylate ranged from 31 to 3254 µg/mL. The correlations between urinary salicylate and 5‐aminosalicylic acid and N‐acetyl‐5‐aminosalicylic acid were 0.96 (95% confidence interval, 0.91–0.98) and 0.9 (95% confidence interval, 0.77–0.96), respectively. Sixteen biopsies were available from 13 patients. The 5‐aminosalicylic acid and N‐acetyl‐5‐aminosalicylic acid concentrations were 0.2–657 ng/mg and 1.6–1598 ng/mg, respectively; there was no correlation with bowel salicylate. Conclusions : The close correlation between 5‐aminosalicylic acid and salicylate levels offers a simple method to assess compliance with 5‐aminosalicylic acid therapy.

Review article: medication non‐adherence in ulcerative colitis – strategies to improve adherence with mesalazine and other maintenance therapies

“…In a study of 98 IBD patients, self‐reporting correctly identified 66% of patients that were non‐adherent, as assessed by urinary drug measurements of 5‐ASA 14 . Urinary salicylate levels correlate positively with urinary 5‐ASA levels, and its measurement has become the standard test in most UK hospitals, representing a simple method for assessing adherence to 5‐ASA therapy 17 . Other methods of ascertaining levels of medication non‐adherence include asking family members, checking prescription uptake at the pharmacist or asking patients to bring their tablets to consultations 17 …”

“…17 Other methods of ascertaining levels of medication nonadherence include asking family members, checking prescription uptake at the pharmacist or asking patients to bring their tablets to consultations. 17…”

Review article: how to control and improve adherence to therapy in inflammatory bowel disease

“…Measurement of drugs, metabolites or both is a more straightforward way to detect adherence. In IBD patients treated with mesalazine, there is a good correlation between urinary mesalazine and urinary salicylate assay, which is widely available 13 . In those who are taking azathioprine or mercaptopurine (mercaptopurine, and MP to 6‐MP), measurement of 6‐thioguanine nucleotides is a possibility, although its use is not widespread.…”

Management of refractory inflammatory bowel disease

“…Direct questioning of patients about compliance is needed, because this information is not volunteered, but even direct questioning may not be fruitful. In selected situations, where the suspicion for noncompliance remains high, urinary salicylate levels and erythrocyte 6-thioguanine nucleotide levels can serve as surrogate markers for 5-ASA agents and purine analogues, respectively [30,64,65]. Recognizing nonadherence and adopting individualized strategies to optimize adherence should be important components in the management of refractory IBD patients.…”