Thiopurine Monotherapy Research Articles

W1915 Further Experience of Optimising Treatment Outcome on Azathioprine by Co-Prescription of Allopurinol in Patients With Inflammatory Bowel Disease

Introduction Many patients, particularly those with high thiopurine methyltransferase (TPMT) activity, preferentially methylate thiopurine drugs, resulting in high levels of methylated metabolites and low thioguanine nucleotides (TGNs). This metabolite pattern is associated with hepatotoxicity and non-response to treatment. Co-prescription of thiopurines (at 25–50% of standard dose) with allopurinol, (which blocks xanthine oxidase) appears to circumvent this problem, optimising both metabolite profile and clinical outcome. Data on the use of allopurinol and thiopurines remain limited. We previously reported our experience of using this combination in thiopurine-related hepatotoxicity. In this study we report further experience for a broader indication, including toxicity (mainly hepatic) non-response with adverse metabolite profile, and very high TPMT activity. Methods Patients prescribed combination treatment were identified from notes in the IBD clinic, TGN monitoring results and hospital pharmacy records. Data were collected retrospectively. We were particularly interested in whether combination treatment overcame the specific problem that precluded thiopurine monotherapy. We also analysed changes in metabolite profiles and subsequent clinical outcome. Results 35 patients have been co-prescribed allopurinol and thiopurines since our previous report. 20 had Crohn9s disease and 15 ulcerative colitis, age range 20–65 years. Their average TPMT activity was 40 pmol/h/mgHb, (vs 32.5 in our population overall). In those receiving co-prescription for adverse effects (14 hepatotoxicity and three other: rash, nausea, fatigue) 94% were able to tolerate combination treatment with complete resolution of liver function tests abnormalities where relevant, of these 88% achieved clinical remission. In 10 patients failing thiopurine monotherapy 50% achieved clinical response on combination treatment. In eight started on combination treatment as primary therapy six (75%) achieved remission, comparing favourably with historical controls. The only adverse event was a transient lymphopaenia in a patient that had mistakenly continued full dose thiopurine. TGN levels increased from an average of 192 to 449 pmol/8×108 RBC on co-treatment, while methylmercaptopurine levels decreased from an average of 503 pmol/8×108 RBC on single agent treatment to just 16 on combination therapy. Conclusion Combination treatment with reduced-dose thiopurine and allopurinol circumvents predominant methylation, optimising metabolite profiles, avoiding hepatotoxicity and improving clinical response. Using combination treatment as first line should lead to a faster remission in those with high TPMT activity. Allopurinol co-prescription may also overcome other side effects. Whether combination therapy should be used first-line in those with high TPMT activity, or more extensively, warrants further investigation in a prospective trial.

PWE-032 Audit of prevention of opportunistic infections in immunosuppressed patients with inflammatory bowel disease: how close are we to the European Crohn's and Colitis Organisation guidelines?: Abstract PWE-032

Introduction The European Crohn's and Colitis Organisation (ECCO) has recently published recommendations on screening and prevention of opportunistic infections in inflammatory bowel disease (IBD) patients. These are based on expert opinion and available evidence, and are more extensive than previous guidelines. The aim of this audit is to compare current practice of screening for, and prevention of, opportunistic infections in our IBD clinic, with these recommendations, and to examine the implications of following the guidelines. Methods IBD patients at risk of opportunistic infections (as defined by ECCO; those treated with thiopurines, methotrexate, anti-TNF or prednisolone>20 mg daily for >2 weeks) were selected consecutively from our IBD clinic and infliximab infusion service from July to November 2009. A data collection sheet was completed for each patient by direct questioning in clinic and by review of patients' records. Information collected included; demographic and clinical details, immunosuppressive medication (IM), screening tests performed (HBsAg, anti-HBs, antiHBc, HCVAb, HIVAb, VZVAb (not applicable (n/a) if history of VZV infection), CXR and cervical smear (females)), and vaccinations given prior to treatment (Hepatits B, VZV (n/a if history of VZV infection), HPV (women<26 years), influenza and Streptococcus pneumoniae). A cost analysis of this screening and vaccination strategy was performed. Results Ninety patients (Crohn's disease (n=70), Ulcerative Colitis (n=19), IBD-unclassified (n=1)) were audited to the time of abstract submission. Of these, 46 were male and 44 female (median age 32 years). Forty-one percent of patients were taking thiopurine monotherapy, 34% concomitant thiopurine and anti-TNF therapy, 14% anti-TNF monotherapy, 6% prednisolone, and 5% methotrexate. The proportion of patients who had recommended screening tests and vaccinations are shown in the table. Patients on anti-TNF therapy were more likely to have undergone CXR, hepatitis B and C screening (p<0.05). The cost of these screening tests and vaccinations (excluding HPV) was GBP£255 per patient (equipment and manpower costs not included) ([Abstract 032][1]). View this table: Abstract PWE-032 Screening tests and vaccinations performed Conclusion Our current practice of screening for and prevention of opportunistic infections in at-risk IBD patients is not in line with recent ECCO recommendations. However, some of the ECCO recommendations are based on limited evidence. Therefore, ongoing audit and research, as well as proof of cost benefit, may be required before they gain widespread acceptance. [1]: #T1