Thiopurine methyl-transferase activity and azathioprine metabolite concentrations do not predict clinical outcome in thiopurine-treated inflammatory bowel disease patients.

BACKGROUND: Low thiopurine-methyl-transferase (TPMT) activity and high 6-thioguanine-nucleotide (6TGN) concentrations have been linked to therapeutic success in inflammatory bowel disease patients treated with thiopurines; however, this has not been implemented in clinical practice. AIM: To identify a therapeutic threshold value for TPMT or 6TGN concentrations, and their capability to predict treatment safety and efficacy. METHODS: Prospective multicentre study including steroid-resistant/dependent patients starting thiopurines. The TPMT activity was determined at inclusion (>5 U/mL required). Azathioprine metabolites [6TGN, 6-methyl-mercaptopurine ribonucleotides (6MMP), and 6TGN/6MMP and 6TGN/TPMT ratios] were periodically monitored during steroid tapering and after withdrawal for 6 months or until a new flare occurred. RESULTS: A total of 113 patients were analysed (62% clinical response). Areas under the receiver operating characteristic (ROC) curve (AUC) relating clinical response and metabolite levels at 2, 4 and 6 months after steroid withdrawal were less than 0.7. The AUCs relating final response and initial TPMT activity or metabolite concentrations at 2, 4, 8 and 16 weeks after starting thiopurines were less than 0.7. No cut-off point with worthwhile sensitivity/specificity was found. Eight (7%) patients developed thiopurine-related toxicity that could not be linked to TPMT activity or 6TGN levels. CONCLUSIONS: Our results do not support determination of TPMT activity or 6TGN concentrations to predict treatment outcome, and no useful serum metabolites threshold value to adjust the drug's dose was identified.

Predictors of response to infliximab in patients with fistulizing Crohn's disease.

OBJECTIVE: To evaluate the efficacy and toxicity of infliximab for the treatment of fistulizing Crohn's disease. METHODS: Consecutive patients with fistulizing Crohn's disease receiving infliximab were prospectively enrolled. Partial response was defined as a reduction of 50% or more from base-line in the number of draining fistulae. Complete response was defined as the closure of all fistulae. The influence of different variables on the efficacy of infliximab was evaluated. RESULTS: 108 patients were included. The disease was inflammatory plus fistulizing in 18% and only fistulizing in 82%. After the third infusion of infliximab the response was partial in 26% and complete in 57%. Response (%) rates (partial/complete) depending on fistula location were: enterocutaneous (25/68%), perianal (35/60%), rectovaginal (36/64%), and enterovesical (20/40%). None of the studied variables (including concomitant immunosuppressive therapy) correlated with efficacy of infliximab in the multivariate analysis. Incidence of adverse effects (21%) depending on the dose of infliximab was: first dose (5.6%), second (7.4%), and third (11.1%). CONCLUSIONS: Infliximab is an efficacious treatment for fistulizing Crohn's disease. Partial response was achieved in approximately one third of the patients, and complete response in more than half. No studied variable was predictive of response. Adverse effects were relatively infrequent and mild.

[Precision and accuracy of the measurement of total cholesterol using the reflectometer Accutrend GC. Usefulness in primary care for diagnosis of hypercholesterolemia]. / Precisión y exactitud de la medida del colesterol total mediante el reflectómetro Accutrend GC. Aplicabilidad en atención primaria para la detección de hipercolesterolemias.

OBJECTIVES: To determine the accuracy and precision of the Accutrend GC (AGC) in measuring cholesterol totals (CT) and its use as a screening test to detect hypercholesterolaemia. DESIGN AND PARTICIPANTS: Venous blood was drawn from 104 patients to measure CT by an enzymatic method (Hitachi 717). At the same time, their capillary blood was also measured with the AGC on two consecutive occasions. Values were divided in three groupings: CT > 149 mg/dl and < or = 199 mg/dl (n = 27); CT > 199 mg/dl and < or = 249 mg/dl (n = 59); and CT > or = 250 mg/dl (n = 18). Accuracy was calculated by obtaining the mean differences (MD) and the confidence intervals of the values obtained with the AGC in the three groupings and comparing them with the values obtained by the laboratory method. Precision was assessed by correlation, the comparison of paired means and the mean coefficient of variation of the values obtained with the AGC in the two successive measurements. MAIN MEASUREMENTS AND FINDINGS: In each grouping the MD of the values obtained with the AGC were lower than those obtained by the laboratory method, respectively. CONCLUSIONS: The AGC is useful as a screening test to detect hypercholesterolaemia, because of its high accuracy and precision. As it also determines glucose it is very useful for diabetics.