BACKGROUND: Infliximab (IFX) is an antitumor necrosis factor (TNF)-α antibody used to treat Crohn's disease (CD). However, antibodies to IFX (ATI) emerge, which can impair its efficacy. A fluid-phase enzyme immunoassay (FP-EIA) was established for measuring serum functional IFX (f-IFX) in CD patients receiving maintenance IFX. METHODS: In 31 patients, 16 had maintained response (GI) and 15 had lost response to IFX despite good initial response (GII) were selected. Serum f-IFX was measured just before and immediately after IFX infusion and the values together with CD activity index (CDAI) and C-reactive protein (CRP) were compared. RESULTS: IFX therapy in GI and GII were 1.8 ± 1.2 years and 2.7 ± 1.5 years, respectively, while the median dose frequency was 56 days in GI and 29 days in GII. Our FP-EIA for f-IFX showed TNF-α binding increasing with the IFX dose, which was suppressed by antibodies to IFX. On the infusion day, CRP and CDAI in GII were significantly higher than in GI, while median trough f-IFX for GI and GII were 4.7 μg/mL and 6.3 μg/mL, respectively. The median f-IFX immediately after IFX infusion for GI and GII were 149.5 μg/mL and 126.3 μg/mL, respectively (P = 0.0488), and binary logistic regression showed conditional maximum likelihood estimate to be -0.0258 (P = 0.0395), supporting association of low postinfusion f-IFX to the loss of response. CONCLUSIONS: FP-EIA could accurately measure f-IFX. High serum ATI strongly impacted f-IFX levels immediately after an infusion. The postinfusion f-IFX level was associated with clinical response. f-IFX level should be valuable in decision-making to optimize treatment efficacy.
BACKGROUND:Infliximab (IFX) is an antitumor necrosis factor (TNF)-α antibody used to treat Crohn's disease (CD). However, antibodies to IFX (ATI) emerge, which can impair its efficacy. A fluid-phase enzyme immunoassay (FP-EIA) was established for measuring serum functional IFX (f-IFX) in CDpatients receiving maintenance IFX. METHODS: In 31 patients, 16 had maintained response (GI) and 15 had lost response to IFX despite good initial response (GII) were selected. Serum f-IFX was measured just before and immediately after IFX infusion and the values together with CD activity index (CDAI) and C-reactive protein (CRP) were compared. RESULTS:IFX therapy in GI and GII were 1.8 ± 1.2 years and 2.7 ± 1.5 years, respectively, while the median dose frequency was 56 days in GI and 29 days in GII. Our FP-EIA for f-IFX showed TNF-α binding increasing with the IFX dose, which was suppressed by antibodies to IFX. On the infusion day, CRP and CDAI in GII were significantly higher than in GI, while median trough f-IFX for GI and GII were 4.7 μg/mL and 6.3 μg/mL, respectively. The median f-IFX immediately after IFX infusion for GI and GII were 149.5 μg/mL and 126.3 μg/mL, respectively (P = 0.0488), and binary logistic regression showed conditional maximum likelihood estimate to be -0.0258 (P = 0.0395), supporting association of low postinfusion f-IFX to the loss of response. CONCLUSIONS: FP-EIA could accurately measure f-IFX. High serum ATI strongly impacted f-IFX levels immediately after an infusion. The postinfusion f-IFX level was associated with clinical response. f-IFX level should be valuable in decision-making to optimize treatment efficacy.
Authors: Byron P Vaughn; Manuel Martinez-Vazquez; Vilas R Patwardhan; Alan C Moss; William J Sandborn; Adam S Cheifetz Journal: Inflamm Bowel Dis Date: 2014-11 Impact factor: 5.325
Authors: Éva Pallagi-Kunstár; Klaudia Farkas; Zoltán Szepes; Ferenc Nagy; Mónika Szűcs; Róbert Kui; Rolland Gyulai; Anita Bálint; Tibor Wittmann; Tamás Molnár Journal: World J Gastroenterol Date: 2014-05-07 Impact factor: 5.742