Intensification with Intravenous Ustekinumab in Refractory Crohn's Disease.

BACKGROUND: The rates of clinical and biochemical responses in Crohn's disease (CD) patients treated with intravenous (IV) ustekinumab (UST) intensification are scarcely described. METHODS: Patients with diagnosis of CD who were under intensified IV ustekinumab treatment (130 mg every 4 weeks) were retrospectively included, evaluating the clinical and biochemical response 12 weeks after the change in treatment regimen (switch from SC to IV), as well as the serum levels of the drug. RESULTS: Twenty-seven patients, all of whom had transitioned to intensified intravenous ustekinumab treatment due to a secondary loss of response to the drug, were included in the retrospective analysis. At the baseline visit, prior to changing IV UST, differences in levels were observed between intensified and non-intensified patients (7216 vs. 2842 ng/mL, p = 0.00005). However, no significant differences were found between these two groups 12 weeks after IV intensification (7949 vs. 7937 ng/mL; p = 0.99). In patients with previous intensified UST SC, a decrease in fecal calprotectin was observed 12 weeks after starting IV intensification, going from a mean of 1463 ug/g to 751 ug/g, although the differences were not significant (p = 0.14). CONCLUSION: In our experience, intensifying treatment with IV UST leads to clinical and biochemical improvements in CD patients with a secondary loss of response to SC maintenance with this drug, and an increase in drug levels was observed 12 weeks after IV UST intensification.

Real-world long-term effectiveness of ustekinumab in ulcerative colitis: results from a spanish open-label cohort.

OBJECTIVE: Ustekinumab was recently approved for the treatment of moderate-to-severe ulcerative colitis (UC). Although data from the UNIFI clinical trial are encouraging, real-world data assessing effectiveness and safety are scarce. The aim of this study was to assess the effectiveness, safety and pharmacokinetics of ustekinumab in a large cohort of refractory UC patients. METHODS: Multicenter observational study of UC patients who received ustekinumab for active disease. The Partial Mayo Score (PMS), endoscopic activity, C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at different time points. Demographic and clinical data, adverse events (AEs) and surgeries were documented. RESULTS: A total of 108 patients were analyzed from 4 referral Spanish hospitals. The clinical remission rates were 59%, 56.5%, 57% and 69% of patients at weeks 8, 16, 24 and 52, respectively. Normalization of FC was achieved in 39.6%, 41% and 51% at weeks 8, 24 and 52, respectively. CRP normalization was observed in 79%, 75% and 76.5% of patients at weeks 8, 24 and 52, respectively. Fewer previous anti-TNF agents and loss of response to anti-TNF were associated with clinical response and normalization of FC, respectively. AEs were observed in 5 patients, and 9 underwent colectomy. Ustekinumab persistence rates were 91%, 83% and 81% at 24, 48 and 96 weeks, respectively. CONCLUSIONS: Ustekinumab demonstrated, in the real-world setting, long-term effectiveness and a favorable safety profile in a cohort of refractory UC patients.

Serologic response to COVID-19 vaccines in patients with inflammatory bowel disease: a prospective study.

BACKGROUND AND AIMS: response to the SARS-CoV-2 vaccine can be altered in patients with immune-mediated diseases, such as inflammatory bowel disease, and in patients under immunosuppressive treatment. The aims of this study were to evaluate the serologic response to the SARS-CoV-2 vaccine in patients with inflammatory bowel disease, to analyze the influence of immunosuppressive drugs on response, and to describe any adverse events in this population. METHODS: this was a prospective study that included adult patients with inflammatory bowel disease. Baseline characteristics, concomitant treatments and previous COVID-19 symptoms were collected. Patients underwent serological testing before the first and after the second vaccine dose. RESULTS: a total of 265 patients were consecutively included. Patients received one of the following vaccines: messenger RNA vaccines from Pfizer/BioNTech and Moderna; and adenovirus vaccines from AstraZeneca and Janssen. All adverse events were mild, and the most frequent was injection site pain in 141 (86 %) patients. The seroconversion rate according to the treatment that patients were receiving was: 100 % for those without treatment, 92.5 % for patients treated with mesalazine, 90.3 % for those receiving immunomodulators, 88.9 % for patients with biological monotherapy and 92.5 % for patients on combined treatment. The generation of antibodies according to the vaccine administered was: Pfizer 92.9 %, Moderna 93.3 %, AstraZeneca 98.4 %, and Janssen 12.5 %. CONCLUSION: the antibody response after vaccination against SARS-CoV-2 is high in patients with inflammatory bowel disease. However, patients treated with immunosuppressive or biologic drugs had a lower response. Adverse events were frequent, but not serious.

Randomized clinical trial evaluating three low-volume preparations for colonoscopy in outpatients with Inflammatory Bowel Disease: the EII-PREP trial.

BACKGROUND: Data regarding bowel preparation in patients with Inflammatory Bowel Disease (IBD) are scarce. AIM: To compare efficacy, safety, and tolerability of low-volume preparations in patients with IBD. METHODS: Single-center, randomized, prescriber, and colonoscopist-blinded clinical trial. IBD outpatients undergoing colonoscopy were randomized 1:1:1 to receive 1 Liter-polyethylene glycol-ascorbate (1L-PEG), 2 Liters-PEG, or sodium picosulfate (SP). The primary endpoint was percentage of quality cleansing assessed via the Boston Bowel Preparation Scale (BBPS ≥6, segments ≥2). Secondary endpoints were total high quality cleansing (BBPS 8 or 9), high-quality segmental BBPS (≥2), and patients' tolerability, symptoms, and satisfaction, assessed by questionnaires. Safety was monitored by adverse event reporting, laboratory evaluation at colonoscopy, and telephonic follow-up. RESULTS: Ninety-two patients were included (33 1L-PEG, 28 2L-PEG, and 31 SP). No significant differences between preparations were observed in quality or high-quality total BBPS or high-quality segmental BBPS. Complete intake of the solution was higher for SP (p = 0.006) and lower for 1L-PEG (p = 0.02) compared to 2L-PEG intake (p = 0.55). Clinically irrelevant hyponatremia was higher in the SP group (p < 0.0001). SP instructions were easier to understand from patient's point of view (p = 0.01). Willingness to retake was higher with SP (p < 0.0001) and less for 1L-PEG (p < 0.0001). No serious adverse events were reported. CONCLUSIONS: We observed no differences in efficacy between low-volume preparations in patients with IBD. Complete intake was higher for SP and lower for 1L-PEG. SP and 2L-PEG instructions were better understood and graded, and SP was more likely to be retaken. Willingness to retake was lower for 1L-PEG. No serious adverse events were reported. SUMMARY: No differences in terms of efficacy were regarded in this clinical trial comparing low-volume preparations for colonoscopy in patients with IBD: however, Sodium Pisoculfate is better tolerated and accepted from patient's point of view. No serious adverse events were reported.

Serologic response to COVID-19 vaccines in patients with inflammatory bowel disease: a prospective study

Background and aims: response to the SARS-CoV-2 vaccine can be altered in patients with immune-mediated diseases, such as inflammatory bowel disease, and in patients under immunosuppressive treatment. The aims of this study were to evaluate the serologic response to the SARS-CoV-2 vaccine in patients with inflammatory bowel disease, to analyze the influence of immunosuppressive drugs on response, and to describe any adverse events in this population. Methods: this was a prospective study that included adult patients with inflammatory bowel disease. Baseline characteristics, concomitant treatments and previous COVID-19 symptoms were collected. Patients underwent serological testing before the first and after the second vaccine dose. Results: a total of 265 patients were consecutively included. Patients received one of the following vaccines: messenger RNA vaccines from Pfizer/BioNTech and Moderna; and adenovirus vaccines from AstraZeneca and Janssen. All adverse events were mild, and the most frequent was injection site pain in 141 (86 %) patients. The seroconversion rate according to the treatment that patients were receiving was: 100 % for those without treatment, 92.5 % for patients treated with mesalazine, 90.3 % for those receiving immunomodulators, 88.9 % for patients with biological monotherapy and 92.5 % for patients on combined treatment. The generation of antibodies according to the vaccine administered was: Pfizer 92.9 %, Moderna 93.3 %, AstraZeneca 98.4 %, and Janssen 12.5 %. Conclusion: the antibody response after vaccination against SARS-CoV-2 is high in patients with inflammatory bowel disease. However, patients treated with immunosuppressive or biologic drugs had a lower response. Adverse events were frequent, but not serious (AU)

Doppler Activity and Ultrasonographic Detection of Intra-Abdominal Fistulas Are Predictors of Surgery in Crohn's Disease.

Bakground and Aim: Predictors of the need for surgery in sticturing Crohn's disease (SCD) are lacking. Bowel ultrasound (US) is a harmless, noninvasive, and inexpensive diagnostic procedure that has proven to be a valuable tool in the management of Crohn's disease (CD). Our aim was to identify ultrasonographic findings in SCD that may associate with a higher risk of surgery, allowing us to make early choices regarding treatment election in this specific group of patients. MATERIALS AND METHODS: This was a retrospective, case-control study. Twenty-four patients diagnosed with SCD between 2013 and 2017 with a past history of stricture-related surgery were included and then matched with 46 non-operated controls. Prior US from patients in both groups were analyzed. US features considered for analysis were as follows: bowel wall thickness, degree of parietal vascularization (measured by Doppler activity), prestenotic dilation, involvement of mesenteric fat, and newly detected concomitant fistulas or abscess. RESULTS: Doppler activity (p < 0.001), enteroenteric fistulas (p = 0.04), enteromesenteric fistulas (p = 0.003), and associated abscess (p = 0.004) were significantly associated with the need for surgery in the short-term period. Multivariate analysis showed strong association of these features with the risk of surgery but failed to reach statistical significance. CONCLUSION: US features may potentially be used as point-of-care tools to aid clinicians in the assessment of the surgical risk in patients with SCD.

Is the degree of i2a recurrence in Crohn's disease secondary to ischemic phenomena?

INTRODUCTION: the Rutgeerts score is used to assess post-surgical recurrence of Crohn's disease (CD). The score initially consisted of four grades, with a subsequent sub-classification of grade 2, under which ulcers confined to the anastomosis (i2a) are considered to be of a probable ischemic origin. The aim of this study was to assess whether ulcers confined to the anastomosis appear at the same frequency in patients undergoing surgery for other causes and can therefore be attributed to post-surgical changes. MATERIAL AND METHODS: this was a retrospective cohort study with patients who had undergone colonoscopy as per clinical practice between 2017 and 2018. There were two cohorts, one cohort of patients to assess the post-surgical recurrence of CD and another cohort for follow-up after colorectal cancer (CRC) treated with ileocolonic anastomosis. RESULTS: a total of 185 patients were included; 33 % had undergone surgery for CD and 67 % had undergone surgery for CRC. Fifty-six percent of patients were male. Of the patients in the group with ulcers confined to the anastomosis, 75 % had CD and 25 % had been operated on for CRC; the difference was statistically significant (p < 0.0001). In turn, of the patients operated on for CRC, 95 % had no anastomotic lesions compared to 18 % of patients with CD. These differences reached statistical significance (p < 0.0001). CONCLUSIONS: In our experience, the occurrence of ulcers on the ileocolonic anastomosis is uncommon in patients that have undergone surgery for CRC, in comparison to patients operated on due to CD. It is possible that these alterations in CD cannot therefore be attributed to solely ischemic or post-surgical phenomena.

Prognostic value of ultrasound activity and parietal healing in patients with Crohn's disease.

INTRODUCTION: the "treat to target" strategy for the management of patients with Crohn's disease (CD) requires simple, reliable and non-invasive tools for continuous monitoring of the disease. Intestinal ultrasound has been proposed as an emerging technique that could be very useful in this field. MATERIAL AND METHODS: patients who had undergone an intestinal ultrasound in the clinical practice between February 2013 and October 2018 at our hospital were retrospectively included. The evolution of the patients during follow-up was assessed based on the presence of ultrasound activity and the therapeutic changes based on the results. RESULTS: two hundred and seventy-seven CD patients were included and the median follow-up time was 24 months (range 5-73 months). Signs of ultrasound inflammatory activity were identified in 166 patients (60 %), and of them, treatment was escalated in 116 patients (70 %) based on the results of the ultrasound. Among patients with identified ultrasound activity, in 166 patients (60 %) the evolution was less favorable than in those without activity, with a shorter time until the next outbreak. Thus, the median disease-free survival (without outbreaks) after performing the ultrasound was 18 months when ultrasound activity was identified (although in most of the patients [70 %] the treatment had been escalated) vs 47 months in patients without ultrasound activity. However, these differences were not statistically significant (p < 0.0001). Among the 111 patients without ultrasound activity, those who achieved "parietal healing" (74 patients) had a better evolution with a 12 % subsequent outbreak vs 27 % during follow-up (p = 0.05). Thus, 15 % of patients with parietal healing had an outbreak vs 34 % of those who had not normalized the ultrasound findings after three years of follow-up. CONCLUSION: intestinal ultrasound is a technique capable of detecting inflammatory activity in patients with Crohn's disease and the presence of ultrasound activity is a risk factor for a new outbreak of activity and/or clinical relapse. Likewise, the presence of "parietal or transmural healing" (PH) is associated with a better evolution of patients during follow-up. Thus, it could be a more precise objective to consider deep remission in CD, with intestinal ultrasound being a useful technique for this purpose.

Infliximab concentrations in two non-switching cohorts of patients with inflammatory bowel disease: originator vs. biosimilar.

Biosimilars are replacing originator compounds due to their similar effectiveness, safety and pharmacokinetics. Our objective was to compare the differences in pharmacokinetics and clinical outcomes between the originator infliximab (Ifx) and the biosimilar CT-P13 in a patient cohort with inflammatory bowel disease (IBD). Our cohort study included 86 patients from a historical and a prospective cohort from the start of infliximab treatment to 22 weeks later. Serum infliximab, antidrug antibody levels and other serum biomarkers were measured at weeks 0, 2, 6, 14 and 22. Remission outcomes were evaluated at weeks 14 and 22. Drug levels were measured prospectively and analysed using MANOVA. Of the 86 patients, 44 (51%) and 42 (49%) were administered the originator and CT-P13, respectively. Originator trough levels were higher than the biosimilar trough levels (35 vs. 21, 20.1 vs. 11, 6.6 vs. 2.9 and 4.3 vs. 1.7 µg/mL at weeks 2, 6, 14 and 22, respectively). A post-hoc analysis demonstrated changes in mean serum drug levels over time (p < 0.001) and according to the drug employed (p = 0.001). At week 22, 13 (81%) patients administered the originator achieved clinical remission compared with 5 (19%) patients with the biosimilar (p = 0.02). None of the patients administered the originator withdrew from the treatment compared with 7 for the biosimilar. During the study, there were significant differences in serum infliximab levels between the originator and the CT-P13 in the patients with IBD. The clinical outcomes were influenced by the type of compound administered.

Management of COVID-19 Pandemic in Spanish Inflammatory Bowel Disease Units: Results From a National Survey.

BACKGROUND: The outbreak of COVID-19 has rapidly evolved into a pandemic that has represented a challenge to health systems worldwide. Inflammatory bowel disease (IBD) units have been forced to change their practices to address the disease and to ensure the quality of care. METHODS: We conducted a national survey among IBD gastroenterologist members of the Spanish Working Group on Crohn's Disease and Colitis regarding changes of practice, IBD treatments, and diagnosis and treatment of COVID-19. RESULTS: We received 54 answers from Spanish hospitals. One hundred percent of the IBD units rescheduled onsite visits to telematic consultation, and elective endoscopic and surgical procedures were delayed. Protective measures were also taken in the infusion units (100% of health centers) and hospital pharmacies, with 40.7% sending subcutaneous medications to patients. No switching between intravenous and subcutaneous anti-tumor necrosis factor drugs were made. We also found that 96.1% of IBD units advised their patients to maintain treatment if they were asymptomatic for COVID-19. For patients with COVID-19 symptoms, 92.6% of IBD units referred them to primary care or the emergency department. In addition, 7.5% of IBD units made a COVID-19 diagnosis through polymerase chain reaction and/or chest x-ray.Modifications in IBD treatment and treatment recommended for COVID-19 are also discussed. CONCLUSIONS: We report a representative national survey of changes made in the structure, diagnosis of COVID-19, and modifications in IBD treatments within IBD units.

Utilidad de la calprotectina sérica como biomarcador de actividad inflamatoria en la enfermedad inflamatoria intestinal / The use of serum calprotectin as a biomarker for inflammatory activity in inflammatory bowel disease

Introducción: para el correcto manejo de la enfermedad inflamatoria intestinal (EII) precisamos de marcadores no invasivos, fiables y sencillos que permitan detectar la actividad inflamatoria de forma precoz. Uno de estos marcadores biológicos podría ser la calprotectina sérica (CS). Material y métodos: inclusión prospectiva de pacientes con EII que iban a realizarse una colonoscopia por práctica clínica habitual. Se determinaron: CS, calprotectina fecal (CF) y parámetros analíticos convencionales. Se realizaron los índices clínicos (Harvey y Walmsley) así como los endoscópicos correspondientes en cada escenario (Simple Endoscopic Score Crohn Disease [SES-CD] y Mayo). Resultados: se incluyeron 53 pacientes; el 51% (27 pacientes) con colitis ulcerosa (CU) y el 49% (26 pacientes) con enfermedad de Crohn (EC). En CU los valores de CS fueron significativamente superiores con actividad endoscópica Mayo 2/3 (mediana 10,39 mg/ml [IQR: 7,4-12,2]) frente aquellos con Mayo 0/1 (mediana 4,07mg/ml [IQR: 2,9-7,2]) (p = 0,01). El área bajo la curva ROC (AUCROC) fue 0,85, obteniendo para un punto de corte de CS de 4,4 mg/dl una sensibilidad y especificidad del 83,3% y 81,25%, respectivamente. Además, al comparar con otros marcadores serológicos de actividad (proteína C reactiva [PCR], velocidad de sedimentación globular [VSG], hemoglobina [Hb] y plaquetas) se obtuvo un AUCROC superior. Cuando comparamos la CS con los hallazgos endoscópicos en EC, no hubo diferencias estadísticamente significativas (SES CD > 3: 20,1 [IQR: 16,8-23,4] vs. SESC ≤ 3:6,25 [IQR: 5,4-7,1]) (p = 0,8). Conclusiones: la CS es un buen marcador indirecto de la actividad inflamatoria y existe correlación con los hallazgos endoscópicos en CU, aunque sin diferencias estadísticamente significativas en EC

Introduction: simple, reliable and non-invasive biomarkers are needed to enable the early detection of inflammatory activity for the correct management of inflammatory bowel disease (IBD). One of these biomarkers may be serum calprotectin (SC). Material and methods: a prospective study was performed of patients with IBD due to undergo a colonoscopy as part of the common clinical practice. The study parameters included SC, fecal calprotectin (FC) and conventional blood test parameters. Clinical indices (Harvey and Walmsley) and relevant endoscopic scores were completed for each scenario (Simple Endoscopic Score Crohn Disease [SES-CD] and Mayo). Results: fifty-three patients were included in the study, 51% (27 patients) with ulcerative colitis (UC) and 49% (26 patients) with Crohn's disease (CD). The CS values in UC were significantly higher with an endoscopic Mayo score 2/3 (median score 10.39 mg/ml [IQR: 7.4-12.2]) compared to those with a Mayo score of 0/1 (median 4.07 mg/ml [IQR: 2.9-7.2]) (p = 0.01). The area under the ROC curve (AUCROC) was 0.85 and the sensitivity and specificity were 83.3% and 81.25%, respectively, for a SC cut-off point of 4.4 mg/dl. Furthermore, a higher AUCROC was obtained in comparison with other serological markers for activity (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], hemoglobin [Hb] and platelets). There were no statistically significant differences in the comparison between SC and endoscopic findings in CD (SES CD > 3: 20.1 [IQR: 16.8-23.4] vs SESC ≤ 3:6.25 [IQR: 5.4-7.1]) (p = 0.8). Conclusions: SC is a good indirect marker of inflammatory activity and there was a correlation with endoscopic findings in UC. However, there were no statistically significant differences in the case of CD

The use of serum calprotectin as a biomarker for inflammatory activity in inflammatory bowel disease.

INTRODUCTION: simple, reliable and non-invasive biomarkers are needed to enable the early detection of inflammatory activity for the correct management of inflammatory bowel disease (IBD). One of these biomarkers may be serum calprotectin (SC). MATERIAL AND METHODS: a prospective study was performed of patients with IBD due to undergo a colonoscopy as part of the common clinical practice. The study parameters included SC, fecal calprotectin (FC) and conventional blood test parameters. Clinical indices (Harvey and Walmsley) and relevant endoscopic scores were completed for each scenario (Simple Endoscopic Score Crohn Disease [SES-CD] and Mayo). RESULTS: fifty-three patients were included in the study, 51% (27 patients) with ulcerative colitis (UC) and 49% (26 patients) with Crohn's disease (CD). The CS values in UC were significantly higher with an endoscopic Mayo score 2/3 (median score 10.39 mg/ml [IQR: 7.4-12.2]) compared to those with a Mayo score of 0/1 (median 4.07 mg/ml [IQR: 2.9-7.2]) (p = 0.01). The area under the ROC curve (AUCROC) was 0.85 and the sensitivity and specificity were 83.3% and 81.25%, respectively, for a SC cut-off point of 4.4 mg/dl. Furthermore, a higher AUCROC was obtained in comparison with other serological markers for activity (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], hemoglobin [Hb] and platelets). There were no statistically significant differences in the comparison between SC and endoscopic findings in CD (SES CD > 3: 20.1 [IQR: 16.8-23.4] vs SESC ≤ 3:6.25 [IQR: 5.4-7.1]) (p = 0.8). CONCLUSIONS: SC is a good indirect marker of inflammatory activity and there was a correlation with endoscopic findings in UC. However, there were no statistically significant differences in the case of CD.

Geographical and occupational aspects of leptospirosis in the coffee-triangle region of Colombia, 2007-2011.

BACKGROUND: There are few studies occupationally profiling as well as using Geographic information system (GIS) to map human leptospirosis. There are no detailed, municipality-level, epidemiological maps in Colombia neither in South America. We developed such maps for the Coffee-triangle region, Colombia and assess some occupational issues. METHODS: surveillance cases data (2007-2011) were used to estimate the annual incidence rates (cases/100,000 population) of leptospirosis to develop the first maps of disease in the 53 municipalities of the Coffee-triangle region of Colombia. GIS used was Kosmo(®) 3.1. Five thematic maps were developed according to municipalities and years. Using labor official information, analyses between agriculture (harvested areas) with disease occurrence was done (linear regression). RESULTS: Between 2007 and 2011, 786 cases were reported (77.8% from one department, Risaralda), for a cumulated rate of 32.18 cases/100,000 population. The highest rate was reported in the less developed municipality of one department (Pueblo Rico, Risaralda) with 1535.05 cases/100,000 population (187 cases, 2009). Armenia (Quindio department capital city), reported 23.41 cases/100,000pop (2011). In those patients with identified occupations, 33.3% were agriculture workers, finding a significant relationship between the number of cases in 2008 and the harvested area by municipality (r(2)=0.48; p=0.0083). CONCLUSION: one of the 53 municipalities contributed with almost a quarter of the cases. Agriculture was significantly associated with the incidence. Use of GIS-based epidemiological maps allow to focus actions in prevention and control for risk zones for leptospirosis which still represents a significant issue in the region and Colombia, particularly in agriculture workers.

High-cylinder acrylic toric intraocular lenses: a case series of eyes with cataracts and large amounts of corneal astigmatism.

PURPOSE: To examine the stability and efficacy of high-cylinder power AcrySof toric intraocular lenses (IOLs), models SN60T6, SN60T7, SN60T8, and SN60T9 (Alcon Laboratories Inc). METHODS: Eligible eyes had cataract and symmetric corneal astigmatism > 2.25 diopters (D). Outcomes included monocular uncorrected distance visual acuity (UDVA), manifest refraction, and assessment of IOL axis. RESULTS: Nineteen eyes from 14 patients had preoperative corneal astigmatism of 4.00 ± 1.10 D. Postoperatively, residual refractive cylinder was 0.55 ± 0.60 D at 3 months. Uncorrected distance visual acuity was 1.3 ± 0.5 logMAR preoperatively and improved to 0.11 ± 0.09 logMAR 3 months postoperatively (P<.0001). All IOLs were stable within 5°. CONCLUSIONS: The IOLs were stable and effective in correcting high amounts of preexisting astigmatism at the time of cataract surgery.