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P262. Patient weight predicts time to loss of response with adalimumab in Crohn's disease

A. Sharma, R. Willert, A. Makin, R. Keld, S. Campbell

Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom

Introduction: Adalimumab (Humira) is a recombinant, monoclonal antibody to tumour necrosis factor (TNF), which is effective in inducing and maintaining remission in Crohn's disease (CD). Unlike Infliximab, adalimumab dosing is not weight specific, and dosing frequency is based on clinical response. Population pharmacokinetic analyses in patients with rheumatoid arthritis have shown that weight has a minimal effect on adalimumab clearance [1]. A detailed medline search revealed no relevant literature relating adalimumab efficacy to patient weight.

Aim: To determine whether weight is important in predicting adalimumab efficacy in Crohn's disease.

Methods: A hospital database of consecutive patients receiving adalimumab therapy for Crohn's disease was retrospectively analysed. A cut off of <80 kg or ≥80 kg was arbitrarily chosen, and time to dose escalation (increased frequency from fortnightly to weekly) and survival according to induction dose were studied in each group. Other data collected included previous infliximab exposure, demographic data, disease anatomy, concomitant immunosuppressive therapy, smoking status and duration of adalimumab therapy.

Results: Data from 62 patients was present on the database (mean age 40.1 years, range 18–74 years; mean weight 71.1 kg, range 45.7–116.3 kg). 47 patients were <80 kg (mean 66.3 kg) and 15 were ≥80 kg (mean 93.1 kg). Both groups were heterogeneous in their Crohn's disease distribution and activity. There was no significant difference between the groups in the duration of adalimumab therapy [<80 kg median 11 months (range 1–39 months) vs. ≥80 kg median 7 months (range 2–27 months), p = 0.52]. Kaplan–Meier estimations revealed a significantly lower time to adalimumab dose escalation in the ≥80 kg cohort (Chi Square 3.9, p = 0.05), a poorer responsiveness in the ≥80 kg cohort at 80/40 mg induction dose [Chi Square 2.3, p = 0.04], and a trend towards poorer responsiveness at 160/80 mg induction dose [Chi Square 2.1, p = 0.07). There was no difference in time to dose escalation according to disease anatomy or smoking status.

Conclusion: Patient weight appears important in predicting adalimumab efficacy in CD with respect to time to dose escalation. In addition, there may be poorer efficacy in patients ≥80 kg, irrespective of induction dosing. Although pharmacokinetic data does not support differences in drug levels according to weight, the mechanism here might be explained by adipokines in overweight CD patients, and their association with a poorer prognosis. A prospective study of the effect of weight on drug response is warranted, incorporating hormonal and anthropometric measurements.

1. Humira Summary of Product Characteristics (SmPC).