PTU-107 Weight adjusted anti-TNF therapy favours obese patients with Crohn's disease

Abstract

was significant intra-individual variation of FC within CD patients, this could impact on the interpretation of single values in isolation. A prospective study to evaluate the degree of variability of FC in three consecutive days stool samples in CD patients in clinical remission was performed. Methods 143 patients with CD in remission (CDAI <150, no escalation of medical therapy within 3 months) who were attending for routine follow-up were identified and enrolled. Patients were excluded if they were taking NSAIDs or developed any change in symptoms over the 3-day collection period. After informed consent, patients were asked to provide stool samples from three consecutive days for analysis. FC was analysed using the Buhlman FC ELISA as per the manufacturer 's instructions. Results Of the 143 patients recruited 34 did not return any samples, 6 returned less than the required number of stool samples, 2 withdrew consent and 2 developed clinical evidence of a flare of disease during the collection period and were excluded from analysis. Therefore 98 complete sets of three stool samples were obtained and analysed. The intraclass correlation coefficient of the 3 FC values, log-transformed, was 0.842 with corresponding 95% CI 0.788 to 0.886 showing that consistency between the three log-transformed FC measurements is high. The reliability of a "normal" FC result of <50 and of <100 was assessed using the k statistic for agreement between the three measurements. For a FC result of <50 k was 0.648 (95% CI 0.508 to 0.770) and for a FC result of <100, k was 0.603 (95% CI 0.483 to 0.712) demonstrating that there is moderately good and similar levels of agreement across the 3 samples for both measures. The reliability of the cut-off of 50 is slightly better than the cut-off of 100. Conclusion The consistency of three faecal calprotectin samples over three consecutive days is high and the CI is narrow suggesting that in a larger population consistency would also be high. This indicates that there is little intra-individual variability of the test and a one off sample can indeed provide reliable information for use in clinical practice. Higher intrapatient variability of high FC values suggests that the log-transformed values are more reliable.

Obesity and response to anti-tumor necrosis factor-α agents in patients with select immune-mediated inflammatory diseases: A systematic review and meta-analysis

“…We included 54 cohorts derived from 50 studies for categorical analysis,[ 14 , 26 – 33 , 40 – 80 ] and 9 cohorts from 8 studies for per-unit dose-response analysis. [ 32 , 33 , 42 , 54 , 81 – 84 ] These included 34 observational cohorts (n = 13,336) and 20 cohorts derived from RCTs (n = 6,036). Fig 1 shows the study selection flowchart.…”

“…[ 14 , 28 – 32 , 40 , 43 , 46 , 57 , 59 – 61 , 67 , 68 , 75 , 78 ] On analysis of studies reporting effect estimates per unit BMI, each 1 kg/m 2 increase in BMI was associated with 6.5% higher odds of failing anti-TNF therapy (9 studies; OR, 1.065 [1.043–1.087], I 2 = 5%) ( S1 Fig ). [ 32 , 33 , 42 , 54 , 81 – 84 ]…”

“…[ 14 , 26 , 28 , 41 , 44 – 46 , 49 – 52 , 60 , 61 , 63 , 65 – 67 , 77 , 78 , 80 ] No significant association was observed between obesity and response to anti-TNF therapy in patients with IBD based on 16 studies, with 3,130 patients (median [IQR], 16.5% [16–24%] obese) (OR, 1.20 [0.88–1.64], I 2 = 50%) ( Fig 7 ), either in patients with CD (12 studies; OR, 1.15 [0.77–1.72]) or ulcerative colitis (4 studies; OR, 1.25 [0.78–2.02]). [ 33 , 42 , 43 , 47 , 48 , 53 , 55 , 58 , 62 , 68 , 69 , 71 – 73 ] Of note, amongst IBD patients, 8/16 studies reported only dichotomous exposure assessment, generally categorized as above or below median weight and as overweight vs. non-overweight categories; more extreme weight categories were not reported.…”

“…Hence, route and dosing scheme could not be evaluated independently. Patients with obesity treated with both weight-based dosing regimens (16 studies; OR, 1.69 [1.26–2.27], I 2 = 67%) (Panel A in S2 Fig )[ 26 , 29 , 30 , 33 , 42 , 43 , 48 , 53 , 54 , 58 , 63 , 64 , 71 – 73 , 79 ] and fixed-dose regimens (31 studies; OR, 1.42 [1.24–1.61], I 2 = 46%) (Panel B in S2 Fig )[ 26 , 27 , 32 , 41 , 42 , 44 – 47 , 52 , 53 , 55 – 57 , 59 – 63 , 65 – 69 , 72 , 73 , 75 – 78 , 80 ] had higher odds of failing therapy, without significant differences in the summary estimate (p-value comparing effect size for fixed-dose and weight-based dosing = 0.28).…”

“…Studies comparing patients with obesity with either non-obese (16 studies, OR, 1.70 [1.32–2.20])[ 26 , 29 , 31 – 33 , 42 , 45 , 47 , 49 – 51 , 63 , 70 , 77 ] or normal BMI (15 studies, OR, 1.94 [1.41–2.68])[ 14 , 27 , 28 , 30 , 43 , 46 , 53 , 57 , 59 , 60 , 64 , 67 , 68 , 75 , 78 ] patients consistently reported a negative effect of obesity on response to therapy; in contrast studies with exposure categories of only overweight vs. non-overweight (without more extreme BMI categories) did not observe a significant association (9 studies; OR, 1.32 [0.82–2.13]) (p interaction = 0.42). [ 33 , 44 , 54 , 55 , 61 , 62 , 72 , 74 , 76 ] Based on outcome definition, the effect of obesity was more pronounced in studies that used validated definitions of clinical remission or response (based on disease activity indices; 39 studies) (failure to achieve remission/response: OR, 1.83 [1.51–2.21])[ 14 , 26 – 32 , 40 , 41 , 44 , 45 , 47 – 52 , 54 ,...…”