Combination therapy in inflammatory bowel disease patients: do we need to maximize the dose of azathioprine?

The use of combination therapy of anti-TNFα 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.

To compare the trough levels, anti-TNFα antibodies and the inflammatory biomarkers between three groups in combotherapy: group 1 (dose of azathioprine <1 mg/kg); group 2 (dose of azathioprine ≥1 and <2 mg/kg), and group 3 (dose of azathioprine ≥2 mg/kg).

A retrospective study was performed, selecting all patients with established diagnosis of IBD who were on combined maintenance treatment.

We included 99 patients, 52.5% female with median age 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 patients treated with IFX, there were no differences in trough levels (p=.976) or formation of antibodies anti-IFX (p=.478) between groups. Moreover, there were no differences in inflammatory biomarkers: CRP (p=.385) and fecal calprotectin (p=.576) among the three groups. Regarding patients treated with ADA, there were no differences in trough levels of ADA (p=.249), formation of antibodies anti-ADA (p=.706) or in inflammatory biomarkers: CRP (p=.738) and fecal calprotectin (p=.269) among the three groups.

In our cohort, there were no differences between anti-TNFα trough levels, formation of anti-TNFα antibodies or inflammatory biomarkers among patients in combotherapy with azathioprine, irrespective of its dosage. In conclusion, our study suggests that maintaining therapeutic levels of anti-TNFα drugs without antibodies formation is feasible with lower doses of azathioprine, minimizing its side effects.