BACKGROUND: Adalimumab (ADA) is a subcutaneous anti-tumour necrosis factor (anti-TNF) agent, effective in inducing and maintaining remission in Crohn's disease (CD). Unlike Infliximab (IFX), ADA dosing is not weight adjusted and dose frequency is based on clinical response. AIM: To determine whether obesity is a risk factor for early loss of response (LOR) to anti-TNF treatment and whether weight-adjusted anti-TNF treatment is favourable. MATERIALS AND METHODS: A hospital database of CD patients receiving anti-TNF treatment was analyzed retrospectively. The relationship between time to LOR and BMI was examined by Kaplan-Meier (KM) survival curves and a Cox proportional hazards model. RESULTS: ADA patients: Of the 54 patients (46 BMI<30 and 8 BMI≥30), KM estimation indicated a significantly shorter time to dose escalation in the BMI of at least 30 (χ=6.117, P=0.01). The Cox proportional hazards model showed that an increased hazard of LOR to ADA is related to increases in BMI (P=0.04). IFX patients: Of the 76 patients (62 BMI<30 and 14 BMI≥30), KM estimation showed that the differences in survival curves were not significant (χ=1.933, P=0.16) for the BMI groups. This was supported by the Cox proportional hazard model (P=0.36). CONCLUSION: BMI appears to be important in predicting ADA efficacy (LOR) in CD. IFX appears to overcome this reduction of efficacy in obese patients. A prospective study evaluating the effect of weight on anti-TNF drug response and serum drug levels is warranted.
BACKGROUND:Adalimumab (ADA) is a subcutaneous anti-tumour necrosis factor (anti-TNF) agent, effective in inducing and maintaining remission in Crohn's disease (CD). Unlike Infliximab (IFX), ADA dosing is not weight adjusted and dose frequency is based on clinical response. AIM: To determine whether obesity is a risk factor for early loss of response (LOR) to anti-TNF treatment and whether weight-adjusted anti-TNF treatment is favourable. MATERIALS AND METHODS: A hospital database of CDpatients receiving anti-TNF treatment was analyzed retrospectively. The relationship between time to LOR and BMI was examined by Kaplan-Meier (KM) survival curves and a Cox proportional hazards model. RESULTS:ADApatients: Of the 54 patients (46 BMI<30 and 8 BMI≥30), KM estimation indicated a significantly shorter time to dose escalation in the BMI of at least 30 (χ=6.117, P=0.01). The Cox proportional hazards model showed that an increased hazard of LOR to ADA is related to increases in BMI (P=0.04). IFXpatients: Of the 76 patients (62 BMI<30 and 14 BMI≥30), KM estimation showed that the differences in survival curves were not significant (χ=1.933, P=0.16) for the BMI groups. This was supported by the Cox proportional hazard model (P=0.36). CONCLUSION: BMI appears to be important in predicting ADA efficacy (LOR) in CD. IFX appears to overcome this reduction of efficacy in obesepatients. A prospective study evaluating the effect of weight on anti-TNF drug response and serum drug levels is warranted.
Authors: Siddharth Singh; Herbert C Heien; Lindsey R Sangaralingham; Stephanie R Schilz; Michael D Kappelman; Nilay D Shah; Edward V Loftus Journal: Clin Gastroenterol Hepatol Date: 2016-04-04 Impact factor: 11.382