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Comparison of efficacy, pharmacokinetics, and immunogenicity between infliximab mono‐ versus combination therapy in ulcerative colitis
Author(s) -
Hayes Michael J,
Stein Adam C,
Sakuraba Atsushi
Publication year - 2014
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12517
Subject(s) - medicine , concomitant , infliximab , ulcerative colitis , azathioprine , pharmacokinetics , gastroenterology , combination therapy , tumor necrosis factor alpha , disease
Background The association of concomitant immunosuppressant use with infliximab ( IFX ) and therapeutic outcomes in correlation with pharmacokinetic properties in ulcerative colitis ( UC ) remains unclear. Aims To assess the effect of concomitant immunosuppressant use on the duration of IFX therapy, and the pharmacokinetic properties of IFX in patients with UC . Methods A retrospective analysis of UC patients treated with IFX . Duration of efficacious IFX therapy, and serum IFX and antibody‐to‐ IFX ( ATI ) levels were compared between those receiving IFX as monotherapy and in combination with an immunosuppressant. Results Among the 85 UC patients who received IFX , 46 (54.1%) received concomitant immunosuppressants, and 38 (45.9%) received IFX monotherapy. Concomitant immunosuppressant use was associated with increased duration of IFX therapy as 90% of patients receiving immunosuppressants remained on therapy at 1 year versus 61% of patients on monotherapy (Log‐rank, P = 0.016). Concomitant immunosuppressant use, as compared with monotherapy, was associated with greater IFX levels (20.4 mg/L vs 10.5 mg/L, P = 0.025) and less frequent ATI formation (4.5% vs 33.3%, P = 0.031). Patients receiving greater than 2.0 mg/kg of azathioprine had greater IFX levels than those receiving less than 2.0 mg/kg (26.0 vs 10.6 mcg/mL, P = 0.03) and those receiving IFX monotherapy (26.0 vs 11.2 mcg/mL, P = 0.03). The duration of IFX therapy among patients receiving less than 2.0 mg/kg azathioprine was indistinguishable from patients on IFX monotherapy (Log‐rank, P = 0.95). Conclusion Concomitant immunosuppressant therapy with IFX improves outcomes in UC as shown by increased duration of therapy, decreased immunogenicity against IFX , and increased blood levels of IFX . Our data suggest that this benefit may be dependent on the dose of concomitant immunosuppression.