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P206. The influence of 5-ASA on thiopurines in Chinese IBD therapy

X. Gao

The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

Aims: To evaluate the influence of 5-ASA on thiopurines in Chinese IBD patients.

Methods: 1. Retrospective study: The history records of patients attending our center from April, 2005 to April, 2010 were reviewed. Recruit criteria: integrity clinical data, duration on AZA/6-MP surpassed three months or treatment discontinued because of adverse effects, co-administrated with 5-ASA over four weeks (mesalazine 3 g/d). 2. Prospective study: Ten IBD patients were on 50 mg AZA daily for four weeks, then on combination therapy with 3 g mesalazine daily for another four weeks. 6-TGN was detected at the end of the 4th week and 8th week.

Results: 139 patients were recruited (93 males; mean age 32±13 yrs; 45 co-treated with 5-ASA and 94 on AZA alone; mean AZA dose 1.7±0.5 mg·kg−1·d−1). 36 patients developed myelotoxicity during AZA/6-MP treatment. (1) Logistic regression analysis was used to elucidate factors associated with myelotoxicity, gastrointestinal intolerance, flu-like symptoms, alopecia and hepatotoxicity. The independent variables were age, gender, disease type (CD/UC), duration on AZA treatment, thiopurine dose and type (AZA/6-MP), co-administration of 5-ASA. Co-administration of mesalazine was the only risk factor significantly associated with myelotoxicity (OR = 3.45, 95%CI 1.31–9.04). (2) 119 patients detected TPMT activity before initiation of AZA/6-MP or co-administration of 5-ASA. The TPMT activity was not significantly different between 36 patients with combination therapy and 83 patients on mono-therapy (12.8±4.7 U/ml RBC vs. 13.1±4.1 U/ml RBC, P = 0.779). The TPMT activity was also not significantly different before and after co-administration of 5-ASA (9.4±3.9 U/ml RBC vs. 10.7±3.6 U/ml RBC, P = 0.527). (3) 127 patients had detected 6-TGN at different time. 382 samples were drawn after four weeks on AZA/6-MP treatment, 73 co-treated with 5-ASA and 309 with AZA alone. ANCOVA showed median 6-TGN was significantly higher in samples co-treated with 5-ASA than those with AZA alone (384.9 pmol/8×108 RBC vs. 286.4 pmol/8×108 RBC, P = 0.00). 14 of 127 patients experienced adding or discontinuing 5-ASA during AZA stable dose treatment, and 6-TGN was higher in patients co-treated with 5-ASA than those after discontinuing 5-ASA for four weeks or before adding 5-ASA (365.8 pmol/8×108 RBC vs 225.6 pmol/8×108 RBC, P = 0.00). (4) Eight of ten patients completed the prospective study. After four weeks on 50 mg AZA daily, seven of eight patients had 6-TGN lower than 230 pmol/8×108 RBC. Then after four weeks co-treated with 3 g mesalazine daily, seven of eight patients had 6-TGN levels higher than 230 pmol/8×108 RBC, three of eight were above 420 pmol/8×108 RBC, and one developed myelotoxicity.

Conclusions: Co-administrated with 5-ASA may result in a higher frequency of myelotoxicity in patients with thiopurines by increasing 6-TGN levels in RBC other than TPMT pathway.

On 50 mg AZA and routine dose 5-ASA, most of the patients had 6-TGN exceed the effective threshold value. This can serve as another reference for AZA dosage adjustment in Chinese patients with or without combination of 5-ASA.