P380 What is the optimal dose of thiopurinic drugs (azatioprine) in patients with inflammatory bowel disease under treatment combined with anti-TNFα (infliximab/adalimumab)?
J. LUCAS RAMOS, C. Suarez Ferrer, M. Sanchez Azofra, J. Poza Cordón, E. Martín Arranz, M.D. Martin Arranz
Gastroenterology, Hospital Universitario La Paz, Madrid, Spain
Background
The combination of anti-TNF drugs with thiopurinic (TPH) drugs in the treatment of IBD, has shown greater clinical efficacy, serum drug levels in therapeutic range in a higher proportion of patients, and less antibody formation, than monotherapy with anti-TNF. However, the dose of the TPH drug in combined treatments has not been clearly established. Some authors consider that this dose could be lower than that used in monotherapy (2.5 mg/kg/day).
Methods
A retrospective study was performed, selecting all patients with the diagnosis of IBD in follow-up at the Hospital La Paz, from 2006 to 2018, who were on combined treatment with azathioprine (AZA) and Anti-TNF. 91 patients were recruited for treatment with infliximab (IF) and 52 for treatment with adalimumab (AD). Two groups were established for both IF and AD, one with the standard dose (2–2.5 mg/kg) and one with a lower dose (less than 2 mg/kg). The main objectives are to evaluate the clinical and pharmacokinetic response: through the measurement of the levels of the biological drug and the formation of anti-drug antibodies (ADA). As secondary variables, PCR and faecal calprotectin are determined
Results
In the AD group, there are no statistically significant differences in remission rates, response without remission, or failure depending on the dose of TPH (adequate or low). There are no differences between PCR and calproctectin levels among patients with optimal doses of TPH and low doses. The last determinations of mean AD levels were not significantly different between groups. No ADA formation was detected. In the IF group, there is no statistically significant difference in remission, response or failure rates depending on the dose of TPH. There are no differences between the levels of PCR and faecal calprotectin, nor in the formation of ADA; nor in the last two determinations of mean IF levels among patients with optimal doses of thiopurines vs. lower doses. If we consider pharmacokinetic failure (infliximab levels < 1000 μg/ml and/or ADA), there were also no statistically significant differences.
| IF (2-2,5 mg/kg) ( | IF (<2 mg/kg) ( | AD (2-2,5 mg/kg) ( | AD (<2 mg/kg) ( | |||
| Serum levels ng/ml (mean) | 2316 | 3484 | 0,08 | 7571 | 8001 | 0.4 |
| Response to treatment (remission/ response / failure) (%) | 40/9/51 | 41/21/ 37 | 0,17 | 66/15/17 | 56/4/3 | 0.83 |
| Anti-drug antibody formation (yes/no) | 41/4 | 42/4 | 0,97 | 0/0 | 0/0 | |
| Faecal calprotectin (mean) | 185 | 237 | 0,52 | 147 | 164 | 0.41 |
Conclusion
Consistent with the findings of other studies, there are no differences in the pharmacokinetic characteristics or in the responses of patients depending on the dose of azathioprine. The use of a lower dose of AZA can provide a better tolerance of the drug, a better safety profile, and lower economic cost.