P0638Excess fat mass is associated with worse outcomes in adults with Crohn’s disease treated with standard dose adalimumab: Body composition analysis of the BIOPIC study

Abstract Background Excess fat mass and myopenia have been associated with adverse disease outcomes in Crohn’s disease (CD). Despite increasing use of advanced therapies in CD, tools that predict treatment response are lacking. We explored if body composition could predict response to standard-dose adalimumab in active CD. Methods This was a secondary analysis of BIOPIC study, a multicentre randomised controlled trial investigating the effect of partial enteral nutrition in patients with active CD commencing adalimumab therapy. Anthropometry and body composition (bioelectrical impedance analysis, Tanita DC-360P) was measured. Fat mass and fat-free mass were standardised for height (body fat index-BFI and fat-free mass index-FFMI). Patient follow-up was undertaken at 6 and 12 weeks to assess response to adalimumab. Clinical response or remission was assessed by Harvey-Bradshaw Index (HBI) and defined as reduction in HBI ≥ 3 or HBI 5. Biochemical response (CRP 10) and faecal calprotectin (FCAL) normalisation (200) were assessed. Therapeutic adalimumab drug levels and anti-drug antibodies (ADAs) were measured. Treatment outcomes and body composition parameters were analysed using logistic regression. Results Seventy-eight participants were included (mean age 40.8 SD 14.5, 41 (53%) female). Baseline BFI (OR 1.24, CI 1.09-1.41, p = 0.001) and fat mass (OR 1.12, CI 1.05-0.19, p = 0.001) were significant predictors of failure to achieve response or remission to adalimumab by week 12 using a univariate logistic regression model; FFMI was not (OR 1.20, CI 0.98-1.46, p = 0.082). There was no correlation between body composition and baseline disease severity indices or biomarkers. Fat mass and BFI remained predictors of failure to achieve response or remission (OR 1.16, CI 1.07-1.26, p = 0.001, OR 1.27, CI 1.03-1.47, p = 0.002 respectively) after adjusting for disease duration, disease severity (HBI), sex and corticosteroid use. Fat mass also predicted failure to normalise CRP (OR 1.07, CI 1.01 – 1.13, p = 0.025) but body composition parameters could not predict normalisation of FCAL. Sixty-six participants had adalimumab drug levels and ADAs measured. Fat mass (%) was negatively correlated with adalimumab drug levels (r = -0.409, p 0.001), positively correlated with ADAs (r = 0.300, p = 0.014) and predicted formation of ADAs to adalimumab (OR 1.07, CI 1.00-1.15, p = 0.043). Conclusion Adiposity predicts risk of treatment failure with standard dose adalimumab. This may be related to suboptimal therapeutic drug levels and increased risk of immunogenicity. Intensive monitoring of therapeutic drug levels and adjustment of adalimumab dose according to adiposity may be considered. Conflict of interest: Dr. Fattah, Sharif: No conflict of interest White, Bernadette: No conflict of interest Campbell, Iona: No conflict of interest Fandinga, Catarina: No conflict of interest Clowe, Jennifer: No conflict of interest Brownson, Emily: No conflict of interest Ho, Gwo-Tzer: No conflict of interest Robertson, Elaine: No conflict of interest Mowat, Craig: No conflict of interest Gaya, Daniel: No conflict of interest Kefayat, Amirhosein: No conflict of interest Din, Shahida: No conflict of interest Seenan, John Paul: No conflict of interest Macdonald, Jonathan: No conflict of interest Gerasimidis, Konstantinos: Grant: Nestle Health Science, Nutricia-Danone, Mylan Personal Fees: Abbott, Baxter, Nestle Health Science, Nutricia-Danone, Servier, Janssen