Su2028 Pinaverium Bromide Plus Symeticone Interacts With the IL-8 +396 GG Variant in the Improvement of Abdominal Pain in IBS. A Report From the Mexican IBS Study Group

Background: IBS is a functional gastrointestinal disorder with a high placebo response; however, Pinaveriumbromide 100mg + Symeticone 300mg bid (PB+S) has shown to improve the severity of abdominal pain and bloating.1-2 Recently, increased IL-8 concentrations have been found in intestinal segments of IBD compared with non-inflamed IBS mucosa,3 and according to our findings, lower IL-8 concentrations are present in unstimulated-cultured PBMCs in IBS vs. controls.4 Additionally, IBS has been associated with the IL-8 intronic variant GG at +396 (rs2227307).5 These results suggest that this cytokine may be related with an inflammatory variant of IBS. Aim: To analyze the association between improvement of abdominal pain in IBS patients treated with PB+S and IL-8 variant rs2227307. Methods: Two-hundred and seventy nine patients with active IBS were randomly allocated to PB+S (n=104) or placebo (n=109), in a 3-month double-blind clinical trial. A 10-cm VAS was used to evaluate the severity of abdominal pain. The rs2227307 was analyzed by QPCR. MANOVA analysis for repeated measurements adjusted by gender, age, BMI and IBS subtype, was performed. A priori multiplicative interaction was considered significant if p,0.20 and for main effects if p,0.05. Results: Mean (+/-SD) age of the population was 36 (+/-9) years and mean BMI 26.5 (+/-5.3). Allele frequencies were T=0.63, G=0.37 and genotypes TT= 38.7%, TG= 48.4% and GG=12.9%. The sample was in HW equilibrium (X2= 0.38, p= 0.54). Abdominal pain improved in patients with the three genotypes with a size effect of 34% (favoring PB+S p=0.004). The larger size effect was in those with GG (70.5%, interaction with treatment p=0.18). Conclusions: This study shows that patients with the rs2227307 do not have the same magnitude of response to placebo compared to those with the other genotypes. We hypothesized that an underlying inflammatory-variant of IBS may be more responsive to PB+S. An effect on mucosal immunological mediators and/or epithelial permeability needs to be elucidated. This study was supported by Takeda-Mexico. References: 1.Schmulson M, et al. Gastroenterology 2011;140(Suppl.1):M1327. 2.Remes-Troche JM. Gastroenterology 2011;140(Suppl.1):M1332. 3.Nielsen OH, et al. Gastroenterol. 1997;32:1028-34. 4.Rodriguez-Fandino O et al. Submitted to DDW 2013. 5. RomeroValdovinos M et al. Mol Biol Rep. 2012 Sep;39(9):8837-43.