Magro F1,2, Lopes SI3, Lopes J4, Portela F5, Cotter J6, Lopes S5, Moreira MJ6, Lago P7, Peixe P8, Albuquerque A3, Rodrigues S3, Silva MR9, Monteiro P10, Lopes C11, Monteiro L12, Macedo G3, Veloso L13, Camila C14,15, Afonso J2,16, Geboes K17, Carneiro F4,18; Portuguese IBD group [GEDII].
1Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar São João, Porto, Portugal Este endereço de email está protegido contra piratas. Necessita ativar o JavaScript para o visualizar..
2Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.
3Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar São João, Porto, Portugal.
4Department of Pathology, Centro Hospitalar São João, Porto, Portugal.
5Department of Gastroenterology, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal.
6Department of Gastroenterology, Centro Hospitalar do Alto Ave, Guimarães, Portugal.
7Department of Gastroenterology, Centro Hospitalar do Porto, Porto, Portugal.
8Department of Gastroenterology, Centro Hospitalar Lisboa Oriental Portugal, Lisboa, Portugal.
9Department of Pathology, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal.
10Department of Pathology, Centro Hospitalar do Alto Ave, Guimarães, Portugal.
11Department of Pathology, Centro Hospitalar do Porto, Porto, Portugal.
12Department of Pathology, Centro Hospitalar Lisboa Oriental Portugal, Lisboa, Portugal.
13Clinical Data Unit, Eurotrials Scientific Consultants, Lisboa, Portugal.
14CIDES Department of Health Information and Decision Sciences, Faculty of Medicine, University of Porto, Porto, Portugal.
15CINTESIS, Center for Health Technology and Services Research, Porto, Portugal.
16MedInUP Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal.
17Department of Pathology, University Hospital of KU Leuven and UZ Gent, Leuven, Belgium.
18Institute of Molecular Pathology and Immunology of the University of Porto [Ipatimup], University of Porto, Porto, Portugal.
ABSTRACT
Background and aims
Histological healing has emerged as a promising therapeutic goal in ulcerative colitis. This is especially important in the context of biological therapies. The objectives of the present study were to investigate the ability of infliximab to induce histological remission in ulcerative colitis [UC] patients and to explore the utility of faecal calprotectin and lactoferrin in predicting histological activity.
Methods
Multi-centre, single-cohort, open-label, 52-week trial including moderately to severely biological-naïve UC patients receiving intravenous infliximab [5mg/kg]. The primary outcome was the proportion of patients with histological remission [Geboes index ≤ 3.0] after 8 weeks of treatment, scored by two independent pathologists.
Results
Twenty patients were included. The rate of histological remission increased from 5% at baseline to 15% and 35% at Week 8 and Week 52, respectively. At Week 8, 40% of patients were in clinical remission [Mayo ≤ 2] and 45% achieved mucosal healing [Mayo endoscopy subscore 0-1]. At Week 52, 25% of patients had clinical, endoscopic and histological remission. Faecal calprotectin and lactoferrin showed the highest correlation with histological activity at Week 8 (area under the curve [AUC] 94%, p = 0.017; and 96%, p = 0.013, respectively) and both markers revealed an excellent positive predictive value for this outcome at this time point [100%, p = 0.017; and 94%, p = 0.013, respectively].
Conclusions
Infliximab was able to induce histological remission. There was a good agreement between histology and faecal biomarkers. Faecal calprotectin and lactoferrin were good predictors of histological remission. Our data support inclusion of histology as a treatment target complementary to endoscopy in clinical trials when evaluating therapeutic response in UC.
