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* = Presenting author

P408 Are pharmacokinetics more unfavourable in inflammatory bowel disease patients aged over 60 years?

L. Rinaldi1, N. Williet*2, E. Del tedesco2, c. Jarlot3, J. M. Phelip2, s. Paul4, X. Roblin3

1Gastroenterology, Saint Etienne, France, 2CHU Saint Etienne, Saint Etienne, France, 3University Hospital, Gastroenterology, Saint Etienne, France, 4University of Saint Etienne, Immunology, Saint Etienne, France

Background

The efficacy of infliximab (IFX) appears to be different depending on the patient’s age with earlier onset of loss of response in patients aged over 60 years.1 Moreover, as for autoimmunity, a more advanced age could be related to decreased immunogenicity. The objectives of this study were to determine if the pharmacokinetics of IFX in patients over 60 years was comparable with those of younger patients, and assess if treatment response in inflammatory bowel disease (IBD) patients is subject to age.

Methods

Patients were selected based on exhaustive pharmacological data from all subjects with IBD treated in our unit, data which were established prospectively. The collection of clinical and laboratory data was carried out on a retrospective basis from the case report forms. We isolated all patients having anti-infliximab antibody (ATI) levels over 100 ng/ml with undetectable IFX trough levels (TRI) (Group A) and compared them with patients exhibiting TRI levels over 2 µg/ml (Group B) and with patients with TRI levels below 0.5 µg/ml associated with ATI below 20 ng/ml (Group C). The assays were performed using an ELISA method (Theradiag, France). Patient was defined as a ‘non-relapser’ if clinical remission was maintained at the last visit and there had been no change in therapy since the last pharmacokinetic analysis.

Results

In total, 110 patients (74 CD; 13 over 60 years) were included: 42 in group A, 42 in group B, and 26 in group C. The proportions of women and of patients with CD were significantly lower in the over-60 group: 7.7% vs 49.5%, (p < 0.01) and 38.4% vs 71.1%, (p = 0.018), respectively. The proportion of patients receiving combination therapy with thiopurines was comparable in the 2 groups (p = 0.11). Further, 24% of patients were in loss of response during follow-up. The time to loss of response to IFX was shorter in the under-60 arm (5 vs 21 months, p = 0.20). Group A patients (ATI > 100 ng/ml) were found more frequently in the over-60 group: 69.2% vs 34.0% (p = 0.014). The time to appearance of ATIs was comparable in the 2 groups 11 vs 6 months (p = 0.18). Univariate analysis revealed 3 factors which were associated with the appearance of high levels of ATI without detectable IFX: age over 60 years (OR 4.36 [1.32–17.09], p = 0.02), CRP > 5 mg/L (OR 2.82 [1.10–7.53], p = 0.033), and calprotectin > 150 µg/g of stool (OR 4.87 [1.12– 24.74], p = 0.021).

Conclusion

In our study the loss of clinical response does not seem to be greater and it occurs later in patients over age 60, compared with those under 60 years, with the appearance of high levels of ATI more frequently and earlier. A combination therapy to avoid an unfavourable pharmacological profile must be discussed in this population.