P551 Combination therapy in IBD Patients: Do we need to maximise the dose of Azathioprine?

C. Arieira1,2,3, F. Dias de Castro1,2,3, T. Cúrdia Gonçalves1,2,3, M.J. Moreira1,2,3, J. Cotter1,2,3

1Hospital da Senhora da Oliveira, Gastroenterology, Guimarães, Portugal, 2Life and Health Sciences Research Institute, School of Medicine, University of Minho, Braga/Guimarães, Portugal, 3ICVS/3B’s, PT Government Associate Laboratory, Braga/Guimarães, Portugal

Background

The use of combination therapy of anti-TNF and thiopurines in inflammatory bowel disease (IBD) is associated with greater efficacy and lower immunogenicity. However, the dose of thiopurine in this setting remains to be elucidated. The aim of the study was to compare the trough levels, anti-TNF antibodies and the inflammatory biomarkers between two groups in combotherapy: one with low dose (LDA) and one with standard dose (SDA) of azathioprine.

Methods

A retrospective study was performed, selecting all patients with an established diagnosis of IBD, who were on combined maintenance treatment (at least 6 months of therapy) with azathioprine and anti-TNF. We divided the population into two groups according to the azathioprine dose: LDA <2 mg/kg and SDA: ≥ 2 mg/kg).

Results

We included 99 patients, 52.5% female with a median age of 33 (17–61) years. Eighty patients (80.8%) were diagnosed with Crohn’s Disease and 19 (19.2%) with ulcerative colitis. Seventy-one (71.8%) patients were on infliximab (IFX) and 28 (28.3%) were on adalimumab (ADA). In the IFX group, there were no differences between trough levels (6.86 vs. 6.70 mg/ml, p = 0.892) or formation of antibodies anti-IFX (6.3% vs. 5.1%; p = 0.838) in SDA vs. LDA. Moreover, there were no differences between inflammatory biomarkers: CRP (p = 0.315) and faecal calprotectin (p = 0.48) among the two groups. Regarding ADA group, there were no differences in trough levels of ADA (10.15 vs. 10.65 mg/ml, p = 0.836), the formation of antibodies anti-ADA (7.7% vs. 6.7%; p = 0.916) and in inflammatory biomarkers: CRP (p = 0.525) and faecal calprotectin (p = 0.496) among the two groups.

Conclusion

In our cohort, there were no differences between anti-TNF trough levels, formation of antibodies anti-TNF and in inflammatory biomarkers among patients in combotherapy with azathioprine in a standard dose vs. lower dose. In terms of immunogenicity, lower doses of azathioprine seem sufficient to inhibit the formation of antibodies, with better tolerance and better safety profile.