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DOP032 Hydrocortisone premedication withdrawal in patients on stable infliximab maintenance: clinical and pharmacokinetic outcomes

Tran-Minh M.-L.*1, Maillet M.1, Auzolle C.1,2, Simon M.3, Cathala A.L.1, Aparicio T.1,2, Baudry C.1, Bonnet J.1, Lourenco N.1, Houze P.4, Gornet J.-M.1, Allez M.1,2

1Saint Louis Hospital, Gastroenterology, Paris, France 2INSERM, U940, Paris, France 3Institut Montsouris, Gastroenterology, Paris, France 4Saint Louis Hospital, Pharmacology, Paris, France

Background

Infliximab (IFX) is effective in maintenance therapy for Crohn's disease (CD) and ulcerative colitis (UC). IFX efficacy may be limited by immunogenicity. It was previously shown that intravenous hydrocortisone premedication reduces IFX antibodies (ATI) formation [1]. This premedication is still now commonly used although its benefit is unclear. The aim of our study was to determine short-term impact of hydrocortisone withdrawal on ATI formation and IFX pharmacokinetic in a cohort of patients treated with IFX.

Methods

Patients were included between February and April 2016. Inclusion criteria were: – diagnosis of CD or UC; – IFX treatment with a stable dose for at least 6 months. Exclusion criteria were: – modification in IFX and/or immunosuppressant dosage; – pregnancy. Hydrocortisone premedication was withdrawn in all patients except during induction phase or if patients had a previous IFX-related infusion reaction. Trough levels and ATIs were measured at each infusion on a one year period (during the 3 infusions preceding and the 3 infusions following hydrocortisone withdrawal).

Results

Hydrocortisone premedication was stopped in 246 patients. One hundred and nine patients were included in the study (median age 36 years-old; 62% men; CD: n=82, UC: n=17). Mean duration of the disease was 13.7 years (1–42). Mean duration of IFX treatment was 5 years. IFX was used in combotherapy in 49 patients (thiopurines: n=39, methotrexate: n=10; mean duration of combotherapy 2 years). IFX treatment was modified after hydrocortisone withdrawal in 14 patients (dose diminution: n=8, optimization: n=5, stop for failure: n=1). Pharmacokinetic analysis was performed in 95 patients who had a stable dose. None of the patients developed permanent ATI, 4 patients had transient ATI and high trough level (>3mcg/ml). Mean IFX trough level before hydrocortisone withdrawal was 5.5 mcg/ml (respectively 4.9, 6.9, 5.1, 5.3 at T-3, T-2, T-1 and T0) and 5.9 mcg/ml after (5.6, 6.0, 6.2 at T+1, T+2, T+3), (NS). There was no significant variation of IFX trough levels, even in patients under monotherapy. Seven patients had symptoms after hydrocortisone withdrawal, without trough level variation and didn't change their treatment. There was no significant variation of CRP (2.55 mg/L versus 2.14 mg/L). None of the patients had IFX related infusion reaction.

Conclusion

In our study, performed in patients on stable IFX maintenance, hydrocortisone discontinuation had no impact on IFX trough levels and was not associated with ATI formation or infusion reactions.

References:

[1] Farrell, (2003), Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial.