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

23 Fev. 2021 |

Cátia Arieira 1 2 3Francisca Dias de Castro 1 2 3Tiago Cúrdia Gonçalves 1 2 3Maria J Moreira 1 2 3José Cotter 1 2 3


Background: 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.

Aim: 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).

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

Results: 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.

Conclusion: 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.