Haggai Bar-Yoseph1, Matti Waterman2, Ronit Almog3, Thomas Billiet4, Séverine Vermeire4, Bella Ungar5, Henit Yanai6, Iris Dotan6, Shomron Ben-Horin5, Yehuda Chowers2. 1. Department of Internal Medicine H, Rambam Health Care Campus and Bruce Rappaport School of Medicine, Technion Israel Institute of Technology, Haifa, Israel. Electronic address: haggaiby@gmail.com. 2. Department of Gastroenterology, Rambam Health Care Campus and Bruce Rappaport School of Medicine, Technion Israel Institute of Technology, Haifa, Israel. 3. Department of Epidemiology, Rambam Health Care Campus and School of Public Health, University of Haifa, Haifa, Israel. 4. Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium. 5. Department of Gastroenterology, Chaim Sheba Medical Center, Ramat-gan and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 6. IBD Center, Department of Gastroenterology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Abstract
BACKGROUND & AIMS: Combination thiopurine-infliximab (IFX) therapy is associated with reduced generation of antidrug antibodies (ADA) compared with IFX monotherapy. Whether past clinical response to thiopurine therapy bears an effect on ADA prevention is unknown. METHODS: This was a retrospective observational multicenter study of patients with Crohn's disease (CD) treated by IFX and thiopurines who had serial ADA measurements. Therapy was classified into past thiopurine response or its lack of, de novo combination, or IFX monotherapy. The primary endpoint was risk of ADA appearance. RESULTS: Out of 494 patients with serial ADA measurements 207 eligible patients were included in the final analysis. The 1-year cumulative risk of ADA development was similar in past thiopurine responders (19.3%) compared with past thiopurine failures (16.1%) (log rank P = .54). ADA was found in 46.6% of the monotherapy group and was significantly different compared with past thiopurine responders (P = .007) and past thiopurine failures (P = .007). The adjusted hazards for ADA development were significantly lower in past responders and past failures compared with the monotherapy group (hazard ratio, 0.47 [95% CI, 0.22-1.00] and 0.32 [95% CI, 0.11-0.93], respectively). CONCLUSIONS: Thiopurines-IFX cotherapy in patients with Crohn's disease is associated with reduced ADA formation compared with IFX monotherapy. This is probably regardless of initial thiopurine therapeutic effect.
BACKGROUND & AIMS: Combination thiopurine-infliximab (IFX) therapy is associated with reduced generation of antidrug antibodies (ADA) compared with IFX monotherapy. Whether past clinical response to thiopurine therapy bears an effect on ADA prevention is unknown. METHODS: This was a retrospective observational multicenter study of patients with Crohn's disease (CD) treated by IFX and thiopurines who had serial ADA measurements. Therapy was classified into past thiopurine response or its lack of, de novo combination, or IFX monotherapy. The primary endpoint was risk of ADA appearance. RESULTS: Out of 494 patients with serial ADA measurements 207 eligible patients were included in the final analysis. The 1-year cumulative risk of ADA development was similar in past thiopurine responders (19.3%) compared with past thiopurine failures (16.1%) (log rank P = .54). ADA was found in 46.6% of the monotherapy group and was significantly different compared with past thiopurine responders (P = .007) and past thiopurine failures (P = .007). The adjusted hazards for ADA development were significantly lower in past responders and past failures compared with the monotherapy group (hazard ratio, 0.47 [95% CI, 0.22-1.00] and 0.32 [95% CI, 0.11-0.93], respectively). CONCLUSIONS:Thiopurines-IFX cotherapy in patients with Crohn's disease is associated with reduced ADA formation compared with IFX monotherapy. This is probably regardless of initial thiopurine therapeutic effect.
Authors: Fotios S Fousekis; Konstantinos Papamichael; Georgios Kourtis; Eleni N Albani; Afroditi Orfanidou; Maria Saridi; Konstantinos H Katsanos; Dimitrios K Christodoulou Journal: Ann Gastroenterol Date: 2021-12-06
Authors: Manon E Wildenberg; Alon D Levin; Alessandro Ceroni; Zhen Guo; Pim J Koelink; Theodorus B M Hakvoort; Liset Westera; Felicia M Bloemendaal; Johannan F Brandse; Alison Simmons; Geert R D'Haens; Daniel Ebner; Gijs R van den Brink Journal: J Crohns Colitis Date: 2017-12-04 Impact factor: 9.071