BACKGROUND: Episodic infliximab (IFX) treatment is associated with the formation of antibodies to IFX (ATIs) in the majority of patients, which can lead to infusion reactions and a shorter duration of response. Concomitant use of immunosuppressives (IS) reduces the risk of ATI formation. AIMS AND METHODS: To investigate which of the IS-that is, methotrexate (MTX) or azathioprine (AZA)-is most effective at reducing the risk of ATI formation, a multicentre cohort of 174 patients with Crohn's disease, treated with IFX in an on-demand schedule, was prospectively studied. Three groups were studied: no IS (n = 59), concomitant MTX (n = 50) and concomitant AZA (n = 65). ATI and IFX concentrations were measured in a blinded manner at Prometheus Laboratories before and 4 weeks after each infusion. RESULTS: ATIs were detected in 55% (96/174) of the patients. The concomitant use of IS therapy (AZA or MTX) was associated with a lower incidence of ATIs (53/115; 46%) compared with patients not taking concomitant IS therapy (43/59; 73%; p<0.001). The incidence of ATIs was not different for the MTX group (44%) compared with the AZA group (48%). Patients not taking IS therapy had lower IFX levels (median 2.42 microg/ml (interquartile range (IQR) 1-10.8), maximum 21 microg/ml) 4 weeks after any follow-up infusion than patients taking concomitant IS therapy (median 6.45 microg/ml (IQR 3-11.6), maximum 21 microg/ml; p = 0.065), but there was no difference between MTX or AZA. In patients who developed significant ATIs >8 microg/ml during follow-up, the IFX levels 4 weeks after the first infusion were retrospectively found to be significantly lower than in patients who did not develop ATIs on follow-up or had inconclusive ATIs. CONCLUSION: Concomitant IS therapy reduces ATI formation associated with IFX treatment and improves the pharmacokinetics of IFX. There is no difference between MTX and AZA in reducing these risks. ATI profoundly influences the pharmacokinetics of IFX. The formation of ATIs >8 microg/ml is associated with lower serum levels of IFX already at 4 weeks after its first administration.
BACKGROUND:Episodic infliximab (IFX) treatment is associated with the formation of antibodies to IFX (ATIs) in the majority of patients, which can lead to infusion reactions and a shorter duration of response. Concomitant use of immunosuppressives (IS) reduces the risk of ATI formation. AIMS AND METHODS: To investigate which of the IS-that is, methotrexate (MTX) or azathioprine (AZA)-is most effective at reducing the risk of ATI formation, a multicentre cohort of 174 patients with Crohn's disease, treated with IFX in an on-demand schedule, was prospectively studied. Three groups were studied: no IS (n = 59), concomitant MTX (n = 50) and concomitant AZA (n = 65). ATI and IFX concentrations were measured in a blinded manner at Prometheus Laboratories before and 4 weeks after each infusion. RESULTS: ATIs were detected in 55% (96/174) of the patients. The concomitant use of IS therapy (AZA or MTX) was associated with a lower incidence of ATIs (53/115; 46%) compared with patients not taking concomitant IS therapy (43/59; 73%; p<0.001). The incidence of ATIs was not different for the MTX group (44%) compared with the AZA group (48%). Patients not taking IS therapy had lower IFX levels (median 2.42 microg/ml (interquartile range (IQR) 1-10.8), maximum 21 microg/ml) 4 weeks after any follow-up infusion than patients taking concomitant IS therapy (median 6.45 microg/ml (IQR 3-11.6), maximum 21 microg/ml; p = 0.065), but there was no difference between MTX or AZA. In patients who developed significant ATIs >8 microg/ml during follow-up, the IFX levels 4 weeks after the first infusion were retrospectively found to be significantly lower than in patients who did not develop ATIs on follow-up or had inconclusive ATIs. CONCLUSION: Concomitant IS therapy reduces ATI formation associated with IFX treatment and improves the pharmacokinetics of IFX. There is no difference between MTX and AZA in reducing these risks. ATI profoundly influences the pharmacokinetics of IFX. The formation of ATIs >8 microg/ml is associated with lower serum levels of IFX already at 4 weeks after its first administration.
Authors: Paul Rutgeerts; William J Sandborn; Brian G Feagan; Walter Reinisch; Allan Olson; Jewel Johanns; Suzanne Travers; Daniel Rachmilewitz; Stephen B Hanauer; Gary R Lichtenstein; Willem J S de Villiers; Daniel Present; Bruce E Sands; Jean Frédéric Colombel Journal: N Engl J Med Date: 2005-12-08 Impact factor: 91.245
Authors: Stephen B Hanauer; Brian G Feagan; Gary R Lichtenstein; Lloyd F Mayer; S Schreiber; Jean Frederic Colombel; Daniel Rachmilewitz; Douglas C Wolf; Allan Olson; Weihang Bao; Paul Rutgeerts Journal: Lancet Date: 2002-05-04 Impact factor: 79.321
Authors: Chong Shen; Philippe Maerten; Karel Geboes; Gert Van Assche; Paul Rutgeerts; Jan L Ceuppens Journal: Clin Immunol Date: 2005-06 Impact factor: 3.969
Authors: C Shen; G V Assche; S Colpaert; P Maerten; K Geboes; P Rutgeerts; J L Ceuppens Journal: Aliment Pharmacol Ther Date: 2005-02-01 Impact factor: 8.171
Authors: Miles P Sparrow; Peter M Irving; Leonard Baidoo; Brian Bressler; Adam S Cheifetz; Shane M Devlin; Laura E Harrell; Jennifer Jones; Patricia L Kozuch; Gil Y Melmed; Fernando S Velayos; Corey A Siegel Journal: Gastroenterol Hepatol (N Y) Date: 2008-10
Authors: Mark T Osterman; Kevin Haynes; Elizabeth Delzell; Jie Zhang; Meenakshi Bewtra; Colleen M Brensinger; Lang Chen; Fenglong Xie; Jeffrey R Curtis; James D Lewis Journal: Clin Gastroenterol Hepatol Date: 2015-02-24 Impact factor: 11.382