OP17The Tasty&Healthy whole food diet improves calprotectin in high risk first-degree relatives of patients with Crohn’s disease (FDRs): The PIONIR randomized controlled prevention cross-over trial

Background With the increasing prevalence of IBD, it becomes vital to explore measures of prevention in individuals at risk. The aim of the PIONIR (Preventing IBD ONset in Individuals at Risk) RCT was to explore the effectiveness of the Tasty&Healthy (T&H) whole food diet in improving biomarkers associated with risk of Crohn’s disease (CD) in high-risk FDRs. Methods We screened 950 healthy FDRs for elevated fecal calprotectin (FC); those with ≥2 tests of > 70µg/g underwent panenteric capsule endoscopy or ileocolonoscopy. Subjects with CD-related mucosal changes (e.g. serpiginous ulcerations) were excluded and the others, categorized in the Potential Pre-CD stage, were randomized to either T&H diet (without formula) or continue their habitual diet for 8 weeks, followed by crossover to the alternate diet for further 8 weeks. FC was measured every 4 weeks. We analyzed the treatment effect using generalized estimating equations (GEE) to account for the two-period, two-sequence crossover design, with fixed effects for treatment, period (1 vs 2), randomization sequence, and baseline FC. All analyses were performed using the ITT approach. Results 28 asymptomatic FDRs with elevated FC but without endoscopic features of CD were randomized (T&H-first n = 13, habitual-first n = 15) with similar baseline characteristics (median FC 211µg/g (IQR 96–254) in the T&H arm vs 182 (73–301) in the habitual arm; p = 0.9). By week 4, median FC dropped to 45µg/g (30–180) in the T&H arm vs. 311µg/g (137–413) in the habitual arm (p = 0.004; Figure). At week 8, median FC was 45 µg/g (33–54) in the T&H arm vs habitual (112µg/g (56–215; p = 0.047). In total, 54% of T&H participants had FC < 50 µg/g after 8-weeks, vs 20% in the habitual diet (RR = 1.73 [95%CI 0.92-3.3]; p = 0.09). Following crossover, participants transitioning from habitual to T&H exhibited a subsequent decline in FC, whereas those transitioning from T&H to habitual showed a return toward higher FC values, both with lesser degree, suggesting a carryover effect of the previous period. In the ITT GEE model that incorporated the entire crossover dataset, FC was 37% lower with the T&H diet vs. the habitual diet, independent of randomization sequence, period, and baseline inflammation (FC ratio=0.63, 95%CI 0.50–0.80, p < 0.001). Conclusion This is the first RCTs that suggests improvement in biomarkers in healthy high-risk FDRs in the Potential Pre-CD stage. T&H diet led to a rapid and significant reduction in intestinal inflammation as reflected by FC compared with habitual diet. Larger trials are needed to evaluate the long-term effect of T&H diet in preventing CD. Conflict of interest: Turner, Dan: Consultation fee: Janssen, Pfizer, Ferring, Abbvie, Takeda, Prometheus Biosciences, Lilly, SorrisoPharma, Boehringer Ingelheim, Galapagos, BMS, AlfaSigma, Merck, Gentech Research support: Janssen, Abbvie, Takeda, Pfizer Royalties: Shaare Zedek Medical Center, Hospital for Sick Children Kenigsberg, Sarah: none Plotkin, Luba: Non Aharoni-Frutkoff, Yonat: No conflict of interest Sokolik, Menachem: none Focht, Gili: Other: Received in the past 3 years consultation fee from Lilly Turpin, Williams: NA Waslyk, Alyssa M: No conflict of interest Ledder, Oren: N/A Griffiths, Anne: Grant: Abbvie Personal Fees: Abbvie, Alfasigma, Amgen, Janssen, Lilly, Merck, Pfizer, Roche, Takeda Martincevic, Inez: N/A Huynh, Hien: Grant: AbbVie and Janssen, Takada Personal Fees: Abbvie adboard Other: Abbvie and Janssen education support Godny, Lihi: Grant: Helmsley Charitable Trust Avni Biron, Irit: N/A Tinoco da Silva Torres, Joana: Grant: Abbvie, Janssen Personal Fees: Pfizer, Janssen, Abbvie, Sandoz, Lilly, Sanofi, Takeda Non-financial Support: Janssen, Abbvie Lee, Sun-Ho: Grant: Sun-Ho Lee is a recipient of the Imagine/ Canadian Institute of Health Research/ Canadian Association of Gastroenterology Fellowship Award. He is also a recipient of the Mount Sinai Hospital Department of Medicine Fellowship Award. Croitoru, Kenneth: N/A