Erythrocyte Mean Corpuscular Volume as a Surrogate Marker for 6-Thioguanine Nucleotide Concentration Monitoring in Patients with Inflammatory Bowel Disease Treated with Azathioprine or 6-Mercaptopurine
Carlton W. ThomasPhilip W. LowryCurtis L. FranklinAmy L. WeaverGennett M. MyhreDennis C. MaysWilliam J. TremaineJames J. LipskyWilliam J. Sandborn
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Mean corpuscular volume may correlate with erythrocyte 6-thioguanine nucleotide concentrations in patients treated with azathioprine and 6-mercaptourine. We conducted a study of 166 patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine to determine the relationship between mean corpuscular volume and erythrocyte 6-thioguanine nucleotide concentrations, disease activity as measured by the Inflammatory Bowel Disease Questionnaire (active disease <170, remission >170), and leukopenia. Blood was submitted for mean corpuscular volume, whole blood 6-thioguanine nucleotide concentration, and leukocyte count. The mean ± SD mean corpuscular volume during treatment was 94.7 ± 6.6 fL and the mean ± SD change in mean corpuscular volume was 7.5 ± 6.3 fL. There were significant correlations between mean corpuscular volume and erythrocyte 6-thioguanine nucleotide concentration (rs = 0.33, p < 0.001) and between change from baseline in mean corpuscular volume and erythrocyte 6-thioguanine nucleotide concentration (rs = 0.26, p = 0.001). There was no correlation between Inflammatory Bowel Disease Questionnaire scores and mean corpuscular volume values (rs = 0.01, p = 0.94). The mean corpuscular volume values in 55 patients with active disease and 111 patients in remission were similar (95.1 vs. 94.5 fL, p = 0.57). There was a weak negative correlation between the mean corpuscular volume and the leukocyte count, (rs = −0.18, p = 0.022). In patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine, mean corpuscular volume and change from baseline in mean corpuscular volume correlated with erythrocyte 6-thioguanine nucleotide concentrations and negatively with leukocyte counts, but did not correlate with disease activity as measured by the Inflammatory Bowel Disease Questionnaire. Measurement of mean corpuscular volume is a simple and inexpensive alternative to measurement of 6-thioguanine nucleotide concentrations in patients treated with azathioprine or 6-mercaptopurine.OBJECTIVE: Azathioprine use in acute ulcerative colitis has been limited by its perceived long onset of action. The aim of this study was to determine the safety and clinical effect of an i.v. loading dose of azathioprine in the setting of severe steroid refractory ulcerative colitis. METHODS: Nine hospitalized patients with severe steroid refractory ulcerative colitis were enrolled. Patients 1–3 received 20 mg/kg i.v. azathioprine over 36 h. Patients 4–6 received 40 mg/kg i.v. azathioprine over 36 h. Patients 7–9 received 40 mg/kg i.v. azathioprine as three 8-h infusions over 3 days. Clinical remission was defined as steroid withdrawal and an Ulcerative Colitis Disease Activity Index score of 0. The Inflammatory Bowel Disease Questionnaire was obtained at each visit. White blood cell concentrations and erthyrocyte concentrations of 6-thioguanine were obtained. RESULTS: Five of nine patients (56%) had a response and avoided colectomy. Three of nine patients (33%) met the definition for clinical remission. Response was seen within 4 wk. The mean 6-thioguanine concentration for those five patients at 12 wk after infusion was 148.2 pmol/8 × 108. Two patients had transient leukopenia and one had transient hepatotoxicity. CONCLUSIONS: Intravenous azathioprine appears to be safe and of clinical benefit in inducing response and avoiding colectomy in severe steroid refractory ulcerative colitis. Data from an i.v. azathioprine trial in Crohn's disease suggests oral dosing alone may obtain the same results. The role of oral dosing alone in severe ulcerative colitis and the role of azathioprine metabolite levels in monitoring efficacy should be investigated further.
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OBJECTIVE: Azathioprine use in acute ulcerative colitis has been limited by its perceived long onset of action. The aim of this study was to determine the safety and clinical effect of an i.v. loading dose of azathioprine in the setting of severe steroid refractory ulcerative colitis. METHODS: Nine hospitalized patients with severe steroid refractory ulcerative colitis were enrolled. Patients 1–3 received 20 mg/kg i.v. azathioprine over 36 h. Patients 4–6 received 40 mg/kg i.v. azathioprine over 36 h. Patients 7–9 received 40 mg/kg i.v. azathioprine as three 8-h infusions over 3 days. Clinical remission was defined as steroid withdrawal and an Ulcerative Colitis Disease Activity Index score of 0. The Inflammatory Bowel Disease Questionnaire was obtained at each visit. White blood cell concentrations and erthyrocyte concentrations of 6-thioguanine were obtained. RESULTS: Five of nine patients (56%) had a response and avoided colectomy. Three of nine patients (33%) met the definition for clinical remission. Response was seen within 4 wk. The mean 6-thioguanine concentration for those five patients at 12 wk after infusion was 148.2 pmol/8 × 108. Two patients had transient leukopenia and one had transient hepatotoxicity. CONCLUSIONS: Intravenous azathioprine appears to be safe and of clinical benefit in inducing response and avoiding colectomy in severe steroid refractory ulcerative colitis. Data from an i.v. azathioprine trial in Crohn's disease suggests oral dosing alone may obtain the same results. The role of oral dosing alone in severe ulcerative colitis and the role of azathioprine metabolite levels in monitoring efficacy should be investigated further.
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Four patients with polymyositis were treated with azathioprine. Each had been treated initially with prednisone and had become unresponsive or suffered severe complications of steroid therapy. Response to azathioprine therapy, as measured by improvement in muscle strength and decrease in serum enzyme levels, was favorable in all patients. Treatment with azathioprine permitted decrease in prednisone dosage with resultant resolution of steroid side effects. No important complications of azathioprine therapy were encountered. We advocate the use of azathioprine in the treatment of polymyositis.
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Objective To observe the levels of plasma P-selection(P-sel) and in patients with ulcerative colitis and to study the clinical significance of them. Methods the concentrations of P-sel in 18 patients with active ulcerative colitis and 13 relief ulcerative colitis were determined with ELISA method. Results The results shown that the levels of P-sel in active ulcerative colitis patients were markedly elevated and were correlated with the severity of the disease. But the levels of P-sel in relief ulcerative colitis patients have no difference with normal controls. Conclusion It is suggested that the occurrence and development of ulcerative colitis may be related to the increase of plasma P-sel. Measurement of levels of plasma P-sel and might therefore provide a tool for monitoring the clinical course and for gaiding the treatment of ulcerative colitis.
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Abstract Twenty‐four patients with myasthenia gravis were treated with azathioprine. Eighteen of the patients tolerated the drug. Six discontinued azathioprine therapy because of toxicity. Of the 18 patients, 15 (83%) improved while receiving azathioprine; in 8 (44%) improvement was felt to result solely from azathioprine. Initial response was seen after 4 to 10 months of treatment, with a mean of 6.4 months. Patients continued to improve for up to 24 months, with the mean time of peak improvement being 14 months. Relapse occurred within one year in all 6 patients in whom azathioprine administration was discontinued. Azathioprine is a reasonable alternative to corticosteroids in selected myasthenic patients requiring immunosuppression.
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