Tratamiento de la enfermedad inflamatoria intestinal refractaria a tratamiento convencional

Malaltia inflamatòria intestinal; Colitis ulcerosa; Malaltia de Crohn; Tractament biològicEnfermedad inflamatoria intestinal; Colitis ulcerosa; Enfermedad de Crohn; Tratamiento biológicoInflammatory bowel disease; Ulcerative colitis; Crohn's disease; Biological treatmentLa malaltia inflamatòria intestinal engloba la colitis ulcerosa i la malaltia de Crohn. Totes dues condicionen un alt impacte en la qualitat de vida i el seu maneig implica elevats costs directes i indirectes. Les opcions terapèutiques per als pacients amb malaltia inflamatòria intestinal han augmentat considerablement en els darrers vint anys. Actualment, disposem de cinc medicaments biotecnològics que actuen en diferents dianes terapèutiques: tres inhibidors del factor de necrosi tumoral (infliximab, adalimumab i golimumab), una antiintegrina a4β7 (vedolizumab) i un anticòs anti-IL-12/23 (ustekinumab). A més, disposem del primer fàrmac sintètic dirigit enfront de la cinasa Janus (tofacitinib) per a la colitis ulcerosa. La incorporació de medicaments biosimilars (actualment, infliximab i adalimumab) ha permès reduir-ne considerablement el cost. En aquest article es revisaran les principals indicacions d’aquests medicaments i els estudis més importants que han permès la seva incorporació en pràctica clínica, així com els principals efectes secundaris.La enfermedad inflamatoria intestinal engloba la colitis ulcerosa y la enfermedad de Crohn. Todas ellas condicionan un alto impacto en la calidad de vida, y su manejo implica elevados costes directos e indirectos. Las opciones terapéuticas, para los pacientes con enfermedad inflamatoria intestinal, han aumentado considerablemente en los últimos veinte años. Actualmente, disponemos de cinco medicamentos biotecnológicos que actúan en diferentes dianas terapéuticas: 3 inhibidores del factor de necrosis tumoral (infliximab, adalimumab y golimumab), una anti-integrina a4β7 (vedolizumab) y un anticuerpo anti-IL12 / 23 (ustekinumab). Además, disponemos del primer fármaco sintético dirigido frente la Janus quinasa (tofacitinib) para la colitis ulcerosa. La incorporación de medicamentos biosimilares (actualmente, de infliximab y adalimumab) ha permitido reducir considerablemente su coste. En este artículo se revisarán las principales indicaciones de estos medicamentos, los estudios más importantes que han permitido su incorporación en práctica clínica, así como los principales efectos secundarios

Usability of a home-based test for the measurement of fecal calprotectin in asymptomatic IBD patients.

The aim of our work was to test the usability of fecal calprotectin (FC) home-based test in inflammatory bowel disease (IBD) patients. METHODS: IBD patients were prospectively recruited. They had to measure FC with a dedicated tool and smartphone application, 5 times at two weeks intervals over an 8 weeks period. They had to fill in a usability questionnaire at the first and the last FC measurement. A System Usability Scale (SUS: 0-100) and the Global Score of Usability (GSU: 0-85) were calculated. FC was also centrally measured by ELISA. RESULTS: Fifty-eight patients were recruited. Forty-two performed at least one FC measurement and 27 performed all the FC requested measurements. The median (IQR) SUS (0-100) at the first and last use were 85 (78-90) and 81 (70-88), respectively; the median (IQR) GSU (0-85) at the first and last use were 74 (69-80) and 77 (68-83), respectively. Adherence to the planned measurements and usability of the tool were higher in females and in less severe disease. The intra-class correlation coefficient between home-based and centrally measured FC was 0.88. CONCLUSION: The adherence to home-based measurement of FC was fair. Usability scores for the home-based test were high. There was a good correlation with the centrally measured FC by ELISA

The use of faecal immunochemical testing in the decision-making process for the endoscopic investigation of iron deficiency anaemia

Background: Blood loss from the gastrointestinal (GI) tract is the most common cause of iron deficiency anaemia (IDA) in adult men and postmenopausal women. Gastroduodenal endoscopy (GDE) and colonoscopy are frequently recommended, despite uncertainty regarding the coexistence of lesions in the upper and lower GI tract. The faecal immunochemical test (FIT) measures the concentration of faecal haemoglobin (f-Hb) originating only from the colon or rectum. We aimed to assess whether the FIT was able to select the best endoscopic procedure for detecting the cause of IDA. Methods: A prospective study of 120 men and postmenopausal women referred for a diagnostic study of IDA were evaluated with an FIT, GDE and colonoscopy. The endoscopic finding of a significant upper lesion (SUL) or a significant bowel lesion (SBL) was considered to be the cause of the IDA. Results: The diagnoses were 35.0% SUL and 20.0% SBL, including 13.3% GI cancer. In the multivariate analysis, the concentration of blood haemoglobin (b-Hb) <9 g/dL (OR: 2.60; 95% CI 1.13-6.00; p = 0.025) and non-steroidal anti-inflammatory drugs NSAIDs (2.56; 1.13-5.88; p = 0.024) were associated with an SUL. Age (0.93; 0.88-0.99; p = 0.042) and f-Hb ≥ 15 μg Hb/g faeces (38.53; 8.60-172.50; p < 0.001) were associated with an SBL. A 'FIT plus gastroscopy' strategy, in which colonoscopy is performed only when f-Hb ≥15 μg Hb/g faeces, would be able to detect 92.4% of lesions and be 100% accurate in the detection of cancer while avoiding 71.6% of colonoscopies. Conclusions The FIT is an accurate method for selecting the best endoscopy study for the evaluation of IDA. An FIT-based strategy is more cost-effective than the current bidirectional endoscopy-based strategy and could improve endoscopic resource allocatio

C4BP(β-)-mediated immunomodulation attenuates inflammation in DSS-induced murine colitis and in myeloid cells from IBD patients

16 p.-9 fig.-1 tab.The most recent and promising therapeutic strategies for inflammatory bowel disease (IBD) have engaged biologics targeting single effector components involved in major steps of the immune-inflammatory processes, such as tumor necrosis factor, interleukins or integrins. Nevertheless, these molecules have not yet met expectations regarding efficacy and safety, resulting in a significant percentage of refractory or relapsing patients. Thus, novel treatment options are urgently needed. The minor isoform of the complement inhibitor C4b-binding protein, C4BP(β-), has been shown to confer a robust anti-inflammatory and immunomodulatory phenotype over inflammatory myeloid cells. Here we show that C4BP(β-)-mediated immunomodulation can significantly attenuate the histopathological traits and preserve the intestinal epithelial integrity in dextran sulfate sodium (DSS)-induced murine colitis. C4BP(β-) downregulated inflammatory transcripts, notably those related to neutrophil activity, mitigated circulating inflammatory effector cytokines and chemokines such as CXCL13, key in generating ectopic lymphoid structures, and, overall, prevented inflammatory immune cell infiltration in the colon of colitic mice. PRP6-HO7, a recombinant curtailed analogue with only immunomodulatory activity, achieved a similar outcome as C4BP(β-), indicating that the therapeutic effect is not due to the complement inhibitory activity. Furthermore, both C4BP(β-) and PRP6-HO7 significantly reduced, with comparable efficacy, the intrinsic and TLR-induced inflammatory markers in myeloid cells from both ulcerative colitis and Crohn’s disease patients, regardless of their medication. Thus, the pleiotropic anti-inflammatory and immunomodulatory activity of PRP6-HO7, able to “reprogram” myeloid cells from the complex inflammatory bowel environment and to restore immune homeostasis, might constitute a promising therapeutic option for IBD.We thank CERCA Programme/Generalitat de Catalunya for institutional support. This work was supported by the Ministerio de Ciencia, Innovación y Universidades (Madrid, Spain) (grants FIS-ISCIII PI20/00464, PI16/00377 and DTS20/00016), and the “Departament de Recerca i Universitats de la Generalitat de Catalunya” (grants 2019PROD00081, 2021INNOV00020, and 2021SGR00521), all co-funded by FEDER funds/European Regional Development Fund (ERDF)-a way to build Europe-. Additionally, the project that gave rise to these results has received funding from the “La Caixa” Foundation and the European Institute of Innovation and Technology, EIT (body of the European Union that receives support from the European Union’s Horizon 2020 research and innovation programme), under the grant agreement CI22–00230. Likewise, this study was financially promoted by the “hna Foundation”. Dr. Vega is supported by the Spanish “Ministerio de Ciencia, Innovación y Universidades/FEDER” [RTI2018–102242-B-I00]. Dr. Rodriguez de Córdoba is supported by the Spanish “Ministerio de Economia y Competitividad/FEDER [SAF2015–66287-R]. Dr. Vega and Dr. Rodriguez de Córdoba are also funded by the Autonomous Region of Madrid [S2022/BMD-7278] and the European Commission – NextGenerationEU through CSIC’s Global Health Platform (”PTI Salud Global”) [SGL2103020].Peer reviewe

Prognostic value of histological activity in patients with ulcerative colitis in deep remission: A prospective multicenter study

Background: Histological remission has been proposed as a new treatment goal in patients with ulcerative colitis (UC) although no universal definition for microscopic activity exists. Aim: We evaluated the accuracy of histological activity to predict clinical relapse in UC patients with both clinical and endoscopic remission. Methods: Asymptomatic UC patients in endoscopic remission (Mayo endoscopic sub-score 0 or 1) undergoing surveillance colonoscopy in two referral hospitals were prospectively recruited. All colonic biopsies were analyzed according to the Geboes' score (GS) and the presence of basal plasmacytosis (BP). Results: Ninety-six patients were included (38% women, median (interquartile range) age 50.0 (39.0-58.5) years, median disease duration 12.0 (6.5-19.5) years). Histological activity defined as GS ≥ 2B.1, GS ≥ 3.1, or BP was present in, respectively, 26%, 23% and 12%. Within 12 months from index endoscopy, 23% of the patients presented with clinical relapse. In multivariate analysis, active histological disease was the only risk factor predicting clinical relapse (odds ratio (95% confidence interval) 4.29 (1.55-11.87); p = 0.005 for GS ≥ 2B.1 and 4.31 (1.52-12.21); p = 0.006 for GS ≥ 3.1). Conclusions: In patients with UC in clinical and endoscopic remission, histological activity is an independent risk factor for clinical relapse. Further prospective studies need to clarify whether treatment optimization is justified in this context.status: publishe

Prognostic value of histological activity in patients with ulcerative colitis in deep remission: A prospective multicenter study

Background: Histological remission has been proposed as a new treatment goal in patients with ulcerative colitis (UC) although no universal definition for microscopic activity exists. Aim: We evaluated the accuracy of histological activity to predict clinical relapse in UC patients with both clinical and endoscopic remission. Methods: Asymptomatic UC patients in endoscopic remission (Mayo endoscopic sub-score 0 or 1) undergoing surveillance colonoscopy in two referral hospitals were prospectively recruited. All colonic biopsies were analyzed according to the Geboes' score (GS) and the presence of basal plasmacytosis (BP). Results: Ninety-six patients were included (38% women, median (interquartile range) age 50.0 (39.0-58.5) years, median disease duration 12.0 (6.5-19.5) years). Histological activity defined as GS >= 2B.1, GS >= 3.1, or BP was present in, respectively, 26%, 23% and 12%. Within 12 months from index endoscopy, 23% of the patients presented with clinical relapse. In multivariate analysis, active histological disease was the only risk factor predicting clinical relapse (odds ratio (95% confidence interval) 4.29 (1.55-11.87); p = 0.005 for GS >= 2B.1 and 4.31 (1.52-12.21); p = 0.006 for GS >= 3.1). Conclusions: In patients with UC in clinical and endoscopic remission, histological activity is an independent risk factor for clinical relapse. Further prospective studies need to clarify whether treatment optimization is justified in this context

Fecal Level of Calprotectin Identifies Histologic Inflammation in Patients With Ulcerative Colitis in Clinical and Endoscopic Remission

BACKGROUND & AIMS: Histologic recovery of patients with ulcerative colitis (UC) often is incomplete, even among those in clinical and endoscopic remission. Persistent active microscopic inflammation is associated with an increased risk of relapse and colorectal neoplasia. A high level of fecal calprotectin (FC) is a reliable marker of endoscopic lesions in patients with UC. We evaluated the accuracy of FC in identifying patients with UC in clinical and endoscopic remission who still have histologic features of inflammation.METHODS: We performed a prospective observational study of 59 patients with UC in clinical and endoscopic remission undergoing colonoscopy. Several biopsy specimens were collected from each colonic segment. Endoscopic remission was defined as a Mayo endoscopic subscore with a grade of 0 or 1. Active histologic inflammation was defined by the presence of neutrophils infiltrating crypt epithelial cells. FC was determined by enzyme-linked immunosorbent assay analysis.RESULTS: Eighteen patients (30.5%) showed evidence of active histologic inflammation. Patients with active histologic inflammation had a significantly higher median level of FC (278 mu g/g; interquartile range, 136-696 mu g/g) than those without active histologic inflammation (68 mu g/g; interquartile range, 30-172 mu g/g) (P = .002). In multivariate analysis, the FC and Mayo endoscopic subscore (0 or 1) were each independent predictors of histologic inflammation. The level of FC identified active histologic inflammation in patients in clinical and endoscopic remission, with an area under the receiver operator characteristic curve value of 0.754.CONCLUSIONS: Histologic inflammation is common among patients with UC in clinical and endoscopic remission. Patients with histologic features of inflammation can be identified reliably based on their fecal level of calprotectin.BACKGROUND & AIMS: Histologic recovery of patients with ulcerative colitis (UC) often is incomplete, even among those in clinical and endoscopic remission. Persistent active microscopic inflammation is associated with an increased risk of relapse and colorectal neoplasia. A high level of fecal calprotectin (FC) is a reliable marker of endoscopic lesions in patients with UC. We evaluated the accuracy of FC in identifying patients with UC in clinical and endoscopic remission who still have histologic features of inflammation.METHODS: We performed a prospective observational study of 59 patients with UC in clinical and endoscopic remission undergoing colonoscopy. Several biopsy specimens were collected from each colonic segment. Endoscopic remission was defined as a Mayo endoscopic subscore with a grade of 0 or 1. Active histologic inflammation was defined by the presence of neutrophils infiltrating crypt epithelial cells. FC was determined by enzyme-linked immunosorbent assay analysis.RESULTS: Eighteen patients (30.5%) showed evidence of active histologic inflammation. Patients with active histologic inflammation had a significantly higher median level of FC (278 mu g/g; interquartile range, 136-696 mu g/g) than those without active histologic inflammation (68 mu g/g; interquartile range, 30-172 mu g/g) (P = .002). In multivariate analysis, the FC and Mayo endoscopic subscore (0 or 1) were each independent predictors of histologic inflammation. The level of FC identified active histologic inflammation in patients in clinical and endoscopic remission, with an area under the receiver operator characteristic curve value of 0.754.CONCLUSIONS: Histologic inflammation is common among patients with UC in clinical and endoscopic remission. Patients with histologic features of inflammation can be identified reliably based on their fecal level of calprotectin.A