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Inflammatory bowel disease II
PTU-107 Weight adjusted anti-TNF therapy favours obese patients with Crohn's disease
  1. M Bhalme1,
  2. A Sharma2,
  3. R Keld3,
  4. A Makin4,
  5. R Willert4,
  6. S Campbell4
  1. 1North Manchester General Hospital, Manchester, Manchester, UK
  2. 2Royal Preston Hospital, Preston, UK
  3. 3Royal Albert Edward Infirmary, Wigan, UK
  4. 4Manchester Royal Infirmary, Manchester, UK

Abstract

Introduction Adalimumab (Humira, Abbott) is a novel subcutaneous anti-TNF agent, effective in inducing and maintaining remission in Crohn's disease (CD). Unlike Infliximab (IFx), Adalimumab (Ad) dosing is not weight adjusted, and dose frequency is based on clinical response. Pharmacokinetic analyses in rheumatoid arthritis patients (pts) has shown weight to have minimal effect on Ad clearance. Our aim was to determine whether weight is important in predicting efficacy of weight adjusted and non-weight adjusted anti-TNF treatment in CD.

Methods A hospital database of CD patients receiving anti-TNF therapy was analysed retrospectively. Demographics, previous IFx exposure, disease anatomy, concomitant immunosuppressive therapy, smoking status and duration of anti-TNF treatment were recorded. A body mass index (BMI) cut off of <30 or ≥30 was used to define obesity and time to dose escalation (increased frequency) and survival curve analysis were compared using Kaplan–Meier (KM) estimation. p<0.05 was taken as significant. Analysis were made using Graphpad prism software.

Results Adalimumab patients: 54 (36 female; age range 17–72 years, median 38.5; BMI range 17.2–47.7, median 24.8) patients details were available. 46 patients had BMI<30 and 8 had BMI≥30. CD distribution and activity were heterogeneous. There was no significant difference (p=NS) in the duration of Ad treatment in BMI<30 (range 1–39 months, median 10.5) vs BMI≥30 (range 6–27 months, median 13.5). KM estimation revealed a significantly lower time to Ad dose escalation in the BMI≥30 (χ2 6.117, p=0.0134). There was no difference in time to dose escalation according to disease anatomy or smoking status. Infliximab patients: 76 (42 female; age range 11–70 years, median 37.5; BMI range 14.9–43.7, median 23.7) patients details were available. 62 patients had BMI<30 and 14 had BMI≥30. CD distribution and activity were heterogeneous. KM estimation revealed the survival curves for the IFx patients were close and statistically non-significant (χ2 1.933, p=NS), in BMI<30 and BMI≥30.

Conclusion Patients BMI appears important in predicting Adalimumab efficacy in CD with respect to loss of response (LOR), irrespective of induction dosing. Weight adjusted anti-TNF treatment appears to overcome this apparent reduction of efficacy in obese patients, as demonstrated by the data. A trend for separation between the two groups may be explained by the additional effects of the pro-inflammatory adipokines in obese patients with CD. A prospective study on the effect of weight on drug response is warranted.

Competing interests None declared.

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