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DOP056. Development of an algorithm incorporating pharmacokinetics of adalimumab in inflammatory bowel diseases

X. Roblin1, M. Rinaudo2,3, E. del Tedesco1, J.M. Phelip1, L. Peyrin Biroulet4, S. Paul3, 1University Hospital, Gastroenterology, Saint Etienne, France, 2University Hospital, Immunology, Saint Etienne, France, 3University of Saint Etienne, Immunology, Saint Etienne, France, 4Brabois Hospital, Gastroenterology, Vandoeuvre les Nancy, France

Background

Several decision algorithms based on the measurement of infliximab (IFX) trough levels and antibodies to infliximab (ATI) have been proposed (1). Whether such algorithms can be extrapolated to the pharmacokinetics of adalimumab (ADA) has yet to be determined.

Methods

A prospective study included all consecutive patients with IBD having a disease flare while being on ADA 40 mg every two weeks monotherapy were included. All patients were primary responders to ADA and anti-TNF naive. ADA trough levels and antibodies to adalimumab (AAA) were measured in blindly to clinical data (Elisa LISA-Tracker, Theradiag). All patients were optimized with ADA 40 mg weekly. Four months later, in the absence of clinical remission [CDAI < 150 for Crohn's disease (CD), and Mayo score <2 for ulcerative colitis (UC)], patients were treated with IFX therapy. Patients were divided into three groups based on ADA trough levels based on previous studies:

Group A: ADA >4.9 microg/mL

Group B: ADA <4.9 microg/mL and undetectable levels of AAA (<10 ng/mL)

Group C: ADA <4.9 microg/mL and AAA >10 microg/mL

Results

82 patients were included (55% CD, mean age 43 years, disease duration 7.4 years, duration of ADA therapy 17 months). After optimization of ADA treatment, 29.2% of patients achieved clinical remission in the group A (N = 41), 67% in the group B (N = 24), and 12% in the group C (N = 17) (p < 0.01 between groups A/B and B/C). CRP level at the time of relapsee, disease duration, duration of ADA therapy and type of IBD were not predictive of clinical remission after optimization by univariate analysis. The response to ADA optimization was significantly more durable in the group B (15 months) than in groups A and C (respectively 4 and 5 months). Fifty-seven patients who failed following ADA optimization (69%) were treated with IFX and 31.6% of them achieved clinical remission. Clinical remission rates following IFX initiation were 12%, 25% and 80% in groups A, B and C (p < 0.01 between groups C/A and C/B), respectively. Duration of response to IFX was significantly higher in the group C than in groups A and B (14 vs. 3 and 5 months, respectively, p < 0.01).

Conclusion

The presence of low ADA trough levels in serum without AAA is strongly predictive of a favorable clinical response after ADA optimization (67%). Conversely low ADA levels with detectable AAA are associated with failure of ADA optimization and a switch to IFX should be considered. ADA trough levels >4.9 µg/mL are associated with clinical response to two anti-TNF (optimisation and switch) in only 10% of cases and must provide an other treatment than anti-TNF (class change).