Konstantinos Papamichael1, Niels Vande Casteele2, Ann Gils2, Sophie Tops2, Scott Hauenstein3, Sharat Singh3, Fred Princen3, Gert Van Assche4, Paul Rutgeerts4, Severine Vermeire4, Marc Ferrante5. 1. Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, Katholieke Universiteit Leuven, Leuven, Belgium; Department of Gastroenterology, Universitair ziekenhuis Leuven, Leuven, Belgium; Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, Leuven, Belgium. 2. Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, Leuven, Belgium. 3. Prometheus Therapeutics and Diagnostics, Laboratories, Inc, San Diego, California. 4. Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, Katholieke Universiteit Leuven, Leuven, Belgium; Department of Gastroenterology, Universitair ziekenhuis Leuven, Leuven, Belgium. 5. Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, Katholieke Universiteit Leuven, Leuven, Belgium; Department of Gastroenterology, Universitair ziekenhuis Leuven, Leuven, Belgium. Electronic address: marc.ferrante@zuleuven.be.
Abstract
BACKGROUND & AIMS: There are limited data on the effects of discontinuing infliximab therapy for Crohn's disease (CD). We investigated the long-term outcome of patients with CD who discontinued infliximab while in clinical remission, and searched for prognostic markers of continued remission after infliximab cessation. METHODS: We performed a retrospective, single-center study of 100 patients with CD who discontinued infliximab upon achieving clinical remission; 84 patients continued immunomodulator therapy. Clinical and endoscopic data were retrieved from a medical database in Belgium, and patients were followed up through April 2013 (median, 9.7 y; interquartile range, 8-11.5 y). Sustained clinical remission (SCR) was defined as maintenance of disease remission, without escalation in medical therapy or CD-related surgeries, until the end of the follow-up period. We measured trough concentrations of infliximab, antibodies to microbial antigens, and circulating inflammatory markers in serum samples collected before treatment and at the time of infliximab discontinuation. RESULTS: At the end of the follow-up period, 52 patients had SCR. Univariate (log-rank) analysis associated SCR with patient age at diagnosis (≥25 y; P = .012) and disease duration (<1 y; P = .017). Among factors evaluated at the time of infliximab discontinuation, infliximab trough concentrations (<6 μg/mL; P = .031), complete mucosal healing (P = .046), and serum positivity for vascular cell adhesion molecule-1 (>0.67 μg/mL; P = .024) were associated with SCR. In multiple Cox proportional hazards regression analysis, only age at diagnosis of 25 years and older was associated independently with SCR (hazard ratio, 1.83; 95% confidence interval, 1.03-3.25; P = .04). CONCLUSIONS: In a large, real-life study, 52% of patients with CD who discontinued infliximab upon achieving clinical remission remained in SCR after a median period of approximately 10 years; Most patients remained on immunomodulator therapy. Although patients with CD have variable responses to infliximab, a subgroup achieved long-term remission after infliximab discontinuation.
BACKGROUND & AIMS: There are limited data on the effects of discontinuing infliximab therapy for Crohn's disease (CD). We investigated the long-term outcome of patients with CD who discontinued infliximab while in clinical remission, and searched for prognostic markers of continued remission after infliximab cessation. METHODS: We performed a retrospective, single-center study of 100 patients with CD who discontinued infliximab upon achieving clinical remission; 84 patients continued immunomodulator therapy. Clinical and endoscopic data were retrieved from a medical database in Belgium, and patients were followed up through April 2013 (median, 9.7 y; interquartile range, 8-11.5 y). Sustained clinical remission (SCR) was defined as maintenance of disease remission, without escalation in medical therapy or CD-related surgeries, until the end of the follow-up period. We measured trough concentrations of infliximab, antibodies to microbial antigens, and circulating inflammatory markers in serum samples collected before treatment and at the time of infliximab discontinuation. RESULTS: At the end of the follow-up period, 52 patients had SCR. Univariate (log-rank) analysis associated SCR with patient age at diagnosis (≥25 y; P = .012) and disease duration (<1 y; P = .017). Among factors evaluated at the time of infliximab discontinuation, infliximab trough concentrations (<6 μg/mL; P = .031), complete mucosal healing (P = .046), and serum positivity for vascular cell adhesion molecule-1 (>0.67 μg/mL; P = .024) were associated with SCR. In multiple Cox proportional hazards regression analysis, only age at diagnosis of 25 years and older was associated independently with SCR (hazard ratio, 1.83; 95% confidence interval, 1.03-3.25; P = .04). CONCLUSIONS: In a large, real-life study, 52% of patients with CD who discontinued infliximab upon achieving clinical remission remained in SCR after a median period of approximately 10 years; Most patients remained on immunomodulator therapy. Although patients with CD have variable responses to infliximab, a subgroup achieved long-term remission after infliximab discontinuation.
Authors: Konstantinos Papamichael; Adam S Cheifetz; Gil Y Melmed; Peter M Irving; Niels Vande Casteele; Patricia L Kozuch; Laura E Raffals; Leonard Baidoo; Brian Bressler; Shane M Devlin; Jennifer Jones; Gilaad G Kaplan; Miles P Sparrow; Fernando S Velayos; Thomas Ullman; Corey A Siegel Journal: Clin Gastroenterol Hepatol Date: 2019-03-27 Impact factor: 11.382
Authors: M J Casanova; M Chaparro; V García-Sánchez; O Nantes; E Leo; M Rojas-Feria; A Jauregui-Amezaga; S García-López; J M Huguet; F Arguelles-Arias; M Aicart; I Marín-Jiménez; M Gómez-García; F Muñoz; M Esteve; L Bujanda; X Cortés; J Tosca; J R Pineda; M Mañosa; J Llaó; J Guardiola; I Pérez-Martínez; C Muñoz; Y González-Lama; J Hinojosa; J M Vázquez; M P Martinez-Montiel; G E Rodríguez; R Pajares; M F García-Sepulcre; A Hernández-Martínez; J L Pérez-Calle; B Beltrán; D Busquets; L Ramos; F Bermejo; J Barrio; M Barreiro-de Acosta; O Roncedo; X Calvet; D Hervías; F Gomollón; M Domínguez-Antonaya; G Alcaín; B Sicilia; C Dueñas; A Gutiérrez; R Lorente-Poyatos; M Domínguez; S Khorrami; C Muñoz; C Taxonera; A Rodríguez-Pérez; A Ponferrada; M Van Domselaar; M L Arias-Rivera; O Merino; E Castro; J M Marrero; M Martín-Arranz; B Botella; L Fernández-Salazar; D Monfort; V Opio; A García-Herola; M Menacho; P Ramírez-de la Piscina; D Ceballos; P Almela; M Navarro-Llavat; V Robles-Alonso; A B Vega-López; I Moraleja; M T Novella; C Castaño-Milla; A Sánchez-Torres; J M Benítez; C Rodríguez; L Castro; E Garrido; E Domènech; E García-Planella; J P Gisbert Journal: Am J Gastroenterol Date: 2016-12-13 Impact factor: 10.864