Abstract Background Antibodies against the integrin αvβ6 has been detected in the serum from inflammatory bowel disease (IBD) patients treated with vedolizumab (VDZ). We aimed to assess the impact of serum αvβ6 antibodies on the pharmacokinetics and the effectiveness of VDZ in IBD. Methods Real-world data were collected from two multicentric, prospective, observational studies, one including patients with IBD treated with VDZ the (VEDOPREDIRESP) and the second one including UC patients treated with intensified golimumab (GOLILOR). Serum αvβ6, antibodies titers were measured prior starting VDZ therapy (baseline) and at week (w)6 (ELISA assay). All clinical datasets and laboratory results were blinded to disease outcomes. Predictors for sustained clinical remission were assessed using univariate tests and multivariate logistic regression. Results During VEDOPREDIRESP, 115 IBD patients (UC, n = 67) were included. At the end of follow-up (W52), 49% of IBD patients (54% for UC) achieved clinical remission. At baseline, abnormal serum αvβ6 antibodies titers (9.1µg/mL based on the median titers + 3 SD from controls) were significantly more frequent in UC than in CD patients (94% vs 19%, respectively; p 0.001) and the median titers were significantly higher in UC patients (271 µg/mL (38-884) vs 5.2 µg/mL (2.5-10); p 0.001). Using a ROC curve analysis, the best threshold value to distinguish UC from CD was 15µg/mL (AUROC : 0.95; Sen : 0.92, Spe : 0.95). In UC, the median serum αvβ6 antibodies titers from patients starting VDZ significantly drop over time between W0 and W6 (243 vs 190 µg/mL, respectively; p = 0.04). During induction regimen with VDZ in UC patients, a reduction of the αvβ6 antibodies titers of more than 30% between W0 and W6 predicted further sustained clinical remission at W52 (AUROC: 0.79; Se: 0.78, Sp : 0.80) (Fig 1). Using multivariate analysis, the only independent factor associated with clinical remission was the reduction of the αvβ6 antibodies titers of more than 30% between W0 and W6 (0R : 5.36, IC95 : 1.12- 8.54; p :0.04). In contrast to VDZ, when using an independent cohort of UC patients treated with golimumab, the median αvβ6 antibodies titers did not differ over time between responders and non-responders to drug intensification. Conclusion Serum αvβ6 antibodies are novel accurate markers to discriminate UC from CD. In UC patients, monitoring serum αvβ6 antibodies titers during induction with VDZ is a strong and drug specific predictor associated with sustained clinical remission at one year and might be of paramount interest to guide clinician’s decision. Conflict of interest: Roblin, Xavier: MSD, Abbvie, Amgen, Celltrion, Galapagos, Janssen, Takeda, Ferring, Theradiag, Lilly, Pfizer Nancey, Stéphane: Abbvie, Janssen, Pfizer, Celltrion, Takeda, Amgen Fresenius Kabi, Sandoz, Lilly XR: MSD, Abbvie, Amgen, Biogen, Celltrion, Galapagos, Janssen, Takeda, Ferring, Theradiag, Lilly Mechi, Fatma: Fumery, Mathurin: Grant: Pfizer Personal Fees: Abbvie, Janssen, Takeda, MSD, Biogen, Amgen, Sandoz, Fresenius, Gilead, Celgene, Galapagos, Mylan, Tillots, Ferring, Pfizer, Hospira, CTMA, Boehringer, Lilly, Arena Non-financial Support: Abbvie, Janssen, Takeda, MSD, Galapagos, Ferring, Pfizer Hebuterne, Xavier: Xavier Hébuterne reports clinical research funding from AbbVie, Abivax, Alphasigma, Arena Pharmaceuticals, Celgene, Eli Lilly, Enterome, Gilead, Janssen, InDex Pharmaceuticals, Pfizer, Roche, Salix, Sangamo, Takeda, Theravance, serving on advisory boards for AbbVie, Abivax, Arena Pharmaceuticals, Gilead, Janssen, Pfizer, Roche, Takeda, and participating in lectures and educational activities for AbbVie, Amgen, Baxter, Fresenius Kabi, Janssen, MSD, Mylan, Nutricia, Pfizer, Tillots, and Takeda. Altwegg, Romain: Abbvie, Celltrion, Janssen, Takeda, MSD, Pfizer Barrau, Mathilde: Abbvie, Celltrion, Takeda, Janssen, Pfizer Paul, Stephane: MSD, Takeda, Abbvie, Amgen, Theradiag, Janssen, Celltrion
Roblin et al. (Thu,) studied this question.