Discontinuation of Infliximab in Patients With Ulcerative Colitis Is Associated With Increased Risk of Relapse: A Multinational Retrospective Cohort Study.
Infliximab is a safe and effective therapy for ulcerative colitis (UC). We conducted a multicenter retrospective cohort study that included 7 European countries and Israel to examine whether infliximab discontinuation can be considered for patients who achieve sustained remission.



We performed a retrospective cohort study, collecting medical records from 13 tertiary care referral inflammatory bowel disease centers of all patients with UC treated with infliximab (n = 193). We compared the disease course of patients with at least 12 months of clinical remission who discontinued infliximab (n = 111) with that of patients who continued scheduled treatment (controls, n = 82). We examined the incidence rates of relapse, hospitalization and colectomy, the comparative effectiveness of different therapeutic strategies after discontinuation, and assessed the rates of response, remission, and adverse effects after infliximab re-initiation. Statistical analyses used time-to-event methods.



In the entire cohort, 67 patients (34.7%) relapsed during the follow-up period. The incidence rate of relapse was significantly higher after discontinuation (23.3 per 100 person-years) compared with the control group (7.2 per 100 person-years) in univariable analysis (log-rank P < .001; hazard ratio, 3.41; 95% confidence interval, 1.88-6.20) and multivariable analysis (hazard ratio, 3.70; 95% confidence interval, 2.02-6.77). Rates of hospitalization and colectomy did not differ between groups. Thiopurines appeared to be the best treatment option after infliximab discontinuation (incidence of relapse: 15.0 per 100 person-years for thiopurines, 27.4 per 100 person-years for thiopurines plus aminosalicylates, and 31.2 per 100 person-years for aminosalicylates alone; log-rank P = .032). Response was regained in 77.1% of patients and remission in 51.4% of patients who re-initiated infliximab. However, 17.1% had infusion reactions and 17.1% reported other adverse events.



In a multinational retrospective cohort study of patients with UC in sustained clinical remission, we associated discontinuation of infliximab with an increased risk of relapse. Treatment re-initiation is effective and safe.
Inflammatory Bowel Disease Center, Department of Gastroenterology, Humanitas Research Hospital, Rozzano, Milan, Italy. Electronic address: gionataf@gmail.com.
Gionata
G
Fiorino
Inflammatory Bowel Disease Unit, Department of Gastroenterology, University Clinic Hospital, Valencia, Spain.
Pablo Navarro
PN
Cortes
Division of Gastroenterology, Mater Dei Hospital, Msida, Malta.
Pierre
P
Ellul
Inflammatory Bowel Disease Unit, Complesso Integrato Columbus, Gemelli Hospital Catholic University, Rome, Italy.
Carla
C
Felice
Department of Gastroenterology, Evangelismos Hospital, Athens, Greece.
Pantelis
P
Karatzas
Department of Gastroenterology, Hospital de São João, Porto, Portugal.
Marco
M
Silva
Semmelweiss University, 1st Department of Internal Medicine, Budapest, Hungary.
Peter L
PL
Lakatos
Unità di Gastroenterologia ed Endoscopia Digestiva, Ospedale Casa Sollievo della Sofferenza, Istituto di Ricovero e Cura a Carattere Scientifico San Giovanni Rotondo (FG), Italy.
Fabrizio
F
Bossa
Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel-Aviv University, Israel.
Bella
B
Ungar
Inflammatory Bowel Disease Unit, Hull and East Yorkshire National Health Service Trust, Hull, United Kingdom.
Shaji
S
Sebastian
Inflammatory Bowel Disease Center, Department of Gastroenterology, Humanitas Research Hospital, Rozzano, Milan, Italy.
Federica
F
Furfaro
Department of Gastroenterology, Venizeleio General Hospital, Heraklion, Crete, Greece.
Konstantinos
K
Karmiris
Division of Gastroenterology, School of Health Sciences, University of Ioannina, Greece.
Konstantinos H
KH
Katsanos
Division of Gastroenterology, Mater Dei Hospital, Msida, Malta.
Martina
M
Muscat
Division of Gastroenterology, School of Health Sciences, University of Ioannina, Greece.
Dimitrios K
DK
Christodoulou
Division of Gastroenterology, Department of Biomedical and Clinical Sciences, Luigi Sacco University Hospital, Milan, Italy.
Giovanni
G
Maconi
Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel-Aviv University, Israel.
Uri
U
Kopylov
Department of Gastroenterology, Hospital de São João, Porto, Portugal; Department of Pharmacology and Therapeutics, Porto Medical School, Porto, Portugal.
Fernando
F
Magro
Department of Gastroenterology, Evangelismos Hospital, Athens, Greece.
Gerassimos J
GJ
Mantzaris
Inflammatory Bowel Disease Unit, Complesso Integrato Columbus, Gemelli Hospital Catholic University, Rome, Italy.
Alessandro
A
Armuzzi
Inflammatory Bowel Disease Unit, Department of Gastroenterology, University Clinic Hospital, Valencia, Spain.
Marta Maia
MM
Boscà-Watts
Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel-Aviv University, Israel.
Shomron
S
Ben-Horin
Inflammatory Bowel Disease Center, Department of Gastroenterology, Humanitas Research Hospital, Rozzano, Milan, Italy.
Stefanos
S
Bonovas
Inflammatory Bowel Disease Center, Department of Gastroenterology, Humanitas Research Hospital, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy.
Silvio
S
Danese
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D005060:Europe; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage*; D006801:Humans; D000069285:Infliximab / Q000008:administration & dosage*; D007557:Israel; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D018570:Risk Assessment; D028761:Withholding Treatment; D055815:Young Adult
D005765:Gastrointestinal Agents; D000069285:Infliximab
Anti-TNF Agent; Discontinuation; IBD; Management; Surgery