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P420. Low dose azathioprine and allopurinol co-therapy: is it safe to use without metabolite monitoring?

B. Eross, H. Johnson, S. Weaver, S. McLaughlin, Royal Bournemouth Hospital, Gastroenterology, Bournemouth, United Kingdom

Background

Low dose azathioprine (AZA)/mercaptopurine (MP) & allopurinol co-therapy (LDAA) is a proven therapeutic option in inflammatory bowel disease (IBD) patients who develop side effects or hepatotoxicity to standard dose AZA/MP. It has been suggested that this combination is not safe to be used without measurement of thiopurine metabolite levels (TML). This is a significant barrier to implementing LDAA.

Aim: To establish whether LDAA therapy is safe without TML measurement.

Methods

We maintain a prospective IBD database. LDAA therapy was introduced in our unit in 2010. Standard dose AZA is given at a dose of 2 mg/kg in TPMT wild-type & 1 mg/kg in heterozygotes. MP dosed at 1 mg/kg & 0.5 mg/kg respectively. LDAA therapy is given at 25% of the standard AZA/MP dose. After commencing LDAA we monitor full blood count (FBC) & liver function test (LFT) weekly for 8 weeks & 3 monthly thereafter. 6-Thioguanine (TGN) & 6-Methyl-MP nucleotide (MMPN) levels checked at 4–16 weeks.

We searched our database for patients who started LDAA. Diagnosis, indications for therapy, FBC, LFT, TML and outcomes were recorded.

Results

76 patients started LDAA, 31 (40.8%) were male. Median age; 47 years (range: 16–79), disease type was: ulcerative colitis (26), Crohn's disease (44), IBD-U (3), microscopic colitis (3). Indications; drug side effects to standard dose AZA/MP, 42; hepatotoxicity, 19; Hypermethylation (MMPN:TGN ratio >11), 9; gout, 4; high TPMT, 2; TML were available in 64 (84%). 11 (14%) stopped LDAA. 9 (12%) due to intolerance, 1 (1%) leucopenia and non-compliant 1 (1%). Median TGN was 375.5 pmol/10*8 red blood cells (RBC) (range: 86–1083) with 6TGN (>250) in 50 (78%). 6MMPN <100 in 23 (30%). The remaining 41 (54%) median 6MMPN level was 170 (range 103–1205). Of the 64 (84%) patients remaining on LDAA at 6 weeks total white cell count <3.5×109/L in 3 patients. LDAA was stopped in 1, dose reduced in 1 and 1 continued LDAA. TGN levels were 275, 483 & 686 pmol/108 RBC. Dose adjustment was made in a further 11 patients following TML; LDAA dose was increased in 9 due to low TGN; median 177 pmol/10*8 RBC (range 97–321) & reduced in 2 due to high TGN (1033 & 790). 2 of 19 patients on LDAA for hepatotoxicity had abnormal LFTs on starting LDAA; 1, autoimmune hepatitis/PSC & 1 under investigation. Neither stopped or reduced LDAA. All patients MMPN was under 5,700 upper limit of normal range at week 6 of LDAA.

Conclusion

In this study decisions regarding stopping LDAA were made based on FBC rather than TML monitoring. TML monitoring was used to ensure adequate dosing. These data therefore suggest that LDAA therapy dosed by weight & TPMT status with weekly FBC monitoring is safe without TML monitoring.