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P444. Infliximab trough levels and antibodies: relationship with infusion reaction, immunomodulators and biological parameters

M.D. Martin Arranz1, E. Martin Arranz1, D. Pascual-Salcedo2, C. De Diego2, M. Jaquotot3, S. Gomez Senent1, J. Poza1, J.M. Suarez Parga1, 1Hospital Universitario La Paz, Gastroenterology, Madrid, Spain, 2Hospital Universitario La Paz, Immunology, Madrid, Spain, 3Rey Juan Carlos University Hospital, Gastroenterology, Madrid, Spain

Background

Infliximab is an anti-TNF drug used to treat inflammatory bowel disease and other disorders. Unfortunately, response failure and side effects are not rate. Determination of trough levels (TL) and Anti-Infliximab antibodies (ATI) has been proposed as a method to optimize antiTNF therapy.

Methods

We included patients receiving induction or maintenance therapy with Infliximab in our Unit between April 2012 and October 2013. Infliximab trough levels were measured by capture ELISA and ATI by a bridging ELISA before each infusion. Clinical response and biological parameters (C-reactive protein, platelet count, haematocrit level and fibrinogen) were also measured.

Infliximab therapy was guided and intensification or drug discontinuation based on clinical criteria.

Results

1101 samples from 126 patients were analysed; 93 Crohn's disease (Montreal classification: A1: 14.6%; A2: 61.8%; A3: 23.6%; L1: 16.1%; L2: 13.8%; L3: 49%; L1+4: 6.9%; L2+4: 6.9%. B1 43.2%; B2 33%; B3 23.9% p 39.8%) and 33 ulcerative colitis (51.6% pancolitis and 48.4% left-sided colitis). Mean age at diagnosis was 31.47 years (SD13.99) and 46.8% males. For patients on scheduled therapy, median time on infliximab prior to the study was 1.69 years (0.1–9).

83.4% patients were antiTNF naïve; 4.8% had received episodic treatment in the past; 69% were under combo therapy with immunomodulators. Mean TL was 5.29 µg/ml (SD 8.48). Twenty-four patients (19.04%) developed ATI. Follow up time was similar between ATI+ and ATI− patients (median 79.14 (Intercuartilic range IR 30.86–177.28) vs 56.5 (22.68–126); p = 0.34).

Ulcerative colitis developed more ATI than Crohn's patients (31.3% vs 14.8% p = 0.043).

ATI development was associated with lack of concomitant immunomodulators (13.4% vs 31%, p = 0.029). The Kaplan–Meier curve showed an early developing of ATI (84.61% during the first year of treatment). No significant difference was observed on time until ATI appearance between combo therapy patients and monotherapy.

ATI+ patients were more prone to infusion reactions (7/24 (29.2%) vs 4/102 (3.9%) p = 0.001). ATI presence was detected prior or in the same day of the infusion reaction in 4 patients and afterwards to the reaction in 3 patients. Interestingly in those patients TL were declining in the previous doses and undetectable at the reaction day.

We observed an inverse relation between trough levels and platelets (p = 0.034), fibrinogen (p = 0.01), also with RCP although not reaching statistical significance (p = 0.07).

Conclusion

Development of ATI is early in the course of treatment, combo therapy prevent its formation even with scheduled treatment but do not affect time of appearance. ATI is associated with infusion reactions. TL are associated with improvement in biological parameters.