Efficacy and safety of biological treatment for inflammatory bowel disease in elderly patients: Results from a GETECCU cohort.

INTRODUCTION: Biological therapies used for the treatment of inflammatory bowel disease (IBD) have shown to be effective and safe, although these results were obtained from studies involving mostly a young population, who are generally included in clinical trials. The aim of our study was to determine the efficacy and safety of the different biological treatments in the elderly population. METHODS: Multicenter study was carried out in the GETECCU group. Patients diagnosed with IBD and aged over 65 years at the time of initiating biological therapy (infliximab, adalimumab, golimumab, ustekinumab or vedolizumab) were retrospectively included. Among the patients included, clinical response was assessed after drug induction (12 weeks of treatment) and at 52 weeks. Patients' colonoscopy data in week 52 were assessment, where available. Regarding complications, development of oncological events during follow-up and infectious processes occurring during biological treatment were collected (excluding bowel infection by cytomegalovirus). RESULTS: A total of 1090 patients were included. After induction, at approximately 12-14 weeks of treatment, 419 patients (39.6%) were in clinical remission, 502 patients (47.4%) had responded without remission and 137 patients (12.9%) had no response. At 52 weeks of treatment 442 patients (57.1%) had achieved clinical remission, 249 patients had responded without remission (32.2%) and 53 patients had no response to the treatment (6.8%). Before 52 weeks, 129 patients (14.8%) had discontinued treatment due to inefficacy, this being significantly higher (p<0.0001) for Golimumab - 9 patients (37.5%) - compared to the other biological treatments analyzed. With respect to tumor development, an oncological event was observed in 74 patients (6.9%): 30 patients (8%) on infliximab, 23 (7.14%) on adalimumab, 3 (11.1%) on golimumab, 10 (6.4%) on ustekinumab, and 8 (3.8%) on vedolizumab. The incidence was significantly lower (p=0.04) for the vedolizumab group compared to other treatments. As regards infections, these occurred in 160 patients during treatment (14.9%), with no differences between the different biologicals used (p=0.61): 61 patients (19.4%) on infliximab, 39 (12.5%) on adalimumab, 5 (17.8%) on golimumab, 22 (14.1%) on ustekinumab, and 34 (16.5%) on vedolizumab. CONCLUSIONS: Biological drug therapies have response rates in elderly patients similar to those described in the general population, Golimumab was the drug that was discontinued most frequently due to inefficacy. In our experience, tumor development was more frequent in patients who used anti-TNF therapies compared to other targets, although its incidence was generally low and that this is in line with younger patients based on previous literature.

Real-World Evidence of Tofacinitib in Ulcerative Colitis: Short-Term and Long-Term Effectiveness and Safety.

INTRODUCTION: The objective of this study was to assess the durability, short-term and long-term effectiveness, and safety of tofacitinib in ulcerative colitis (UC) in clinical practice. METHODS: This is a retrospective multicenter study including patients with UC who had received the first tofacitinib dose at least 8 weeks before the inclusion. Clinical effectiveness was based on partial Mayo score. RESULTS: A total of 408 patients were included. Of them, 184 (45%) withdrew tofacitinib during follow-up (mean = 18 months). The probability of maintaining tofacitinib was 67% at 6 m, 58% at 12 m, and 49% at 24 m. The main reason for tofacitinib withdrawal was primary nonresponse (44%). Older age at the start of tofacitinib and a higher severity of clinical activity were associated with tofacitinib withdrawal. The proportion of patients in remission was 38% at week 4, 45% at week 8, and 47% at week 16. Having moderate-to-severe vs mild disease activity at baseline and older age at tofacitinib start were associated with a lower and higher likelihood of remission at week 8, respectively. Of 171 patients in remission at week 8, 83 (49%) relapsed. The probability of maintaining response was 66% at 6 m and 54% at 12 m. There were 93 adverse events related to tofacitinib treatment (including 2 pulmonary thromboembolisms [in patients with risk factors] and 2 peripheral vascular thrombosis), and 29 led to tofacitinib discontinuation. DISCUSSION: Tofacitinib is effective in both short-term and long-term in patients with UC. The safety profile is similar to that previously reported.

Intermittent boluses versus pump continuous infusion for endoscopist-directed propofol administration in colonoscopy.

BACKGROUND: non-anesthesiologist administration of propofol (NAAP) using continuous infusion systems may achieve a more sustained sedative action. AIM: to compare intermittent boluses (IB) with pump continuous infusion (PCI) for NAAP, targeted to moderate sedation, for colonoscopy. METHODS: 192 consecutive outpatients were randomized to receive IB (20 mg propofol boluses on demand) or PCI (3 mg/kg/h plus 20 mg boluses on demand). Sedation could be stopped at cecal intubation at the discretion of the endoscopist. Satisfaction rates of the patient, nurses and endoscopist, propofol doses, depth of sedation (at the beginning, at cecal intubation and at the end), recovery times, complications and were collected. RESULTS: there were no differences between groups regarding patient, nurse or endoscopist satisfaction rates with procedural sedation. Propofol doses (mg) were significantly higher during the induction phase -86 (30-172) vs. 78 [30-160], p 0.03- and overall -185 (72-400) vs. 157 (60-460), p = 0.003- for PCI group. 81 % of assessments of the depth of sedation were moderate. The level of sedation (O/AAS scale) was borderline significantly deeper at cecal intubation (2.38 vs. 2.72; p = 0.056) and at the end of the procedure (4.13 vs. 4.45; p = 0.05) for PCI group, prolonging thus early recovery time (6.3 vs. 5.1 minutes, p = 0.008), but not discharge time. Complications, all of them in minors, were non-significantly more frequent in the PCI group (9 vs. 7 %, p = 0.07). CONCLUSIONS: NAAP for colonoscopy was safely administered with comparable satisfaction and complication rates with either IB or PCI.

[Split-dose sodium picosulphate/magnesium citrate for morning colonoscopies performed 2 to 6 hours after fluid intake]. / Preparación con picosulfato sódico/citrato de magnesio en dosis fraccionadas para colonoscopias en turno de mañana realizadas entre las 2 y 6 horas posteriores a la ingesta de líquidos.

BACKGROUND: Split dosage of bowel preparations has been shown to substantially improve bowel cleansing. AIM: To compare the split dose (SD) sodium picosulphate/magnesium oxide/anhydrous citric acid (Citrafleet(®)) regimen for morning colonoscopies with standard cleansing the day before. METHODS: Consecutive outpatients were randomized to receive Citrafleet(®) the day before colonoscopy or SD, in whom the second half was administered on an individual basis from 2 to 6 hours before the procedure. No bisacodyl was administered. All procedures were performed with non-anesthesiologist administered propofol sedation. The Boston scale was used to assess the quality of bowel preparation (adequate cleansing if score ≥ 6, with no score of 0/1 in any segment). RESULTS: A total of 193 patients were included. Overall bowel cleansing was significantly better in the SD group (7 vs. 5.2, p<0.001), as well as in the cecum (2.4 vs. 1.4, p < 0.001), ascending colon (2.5 vs. 1.6, p<0.001) and transverse colon (2.4 vs. 2, p=0.004). A significant proportion of SD patients had adequate bowel cleansing (71% vs. 30%, p<0.001). Patients in the SD group drank a greater amount of liquid (4.9 vs. 4 liters, p=0.006) and more frequently perceived the cleansing process to be easy or very easy to complete (89 vs. 68%, p=0.04), although they slept significantly fewer hours (6.5 vs. 7.9, p<0.001). No bronchoaspiration pneumonia was reported. CONCLUSIONS: SD Citrafleet(®) 2 to 6 hours before colonoscopy increased the rate of procedures with adequate bowel cleansing by 40%, especially in the proximal colon, allowed more liquids to be drunk and increased the perception of ease in completing the preparation, with no sedation-related complications.

Nonbismuth quadruple (concomitant) therapy: empirical and tailored efficacy versus standard triple therapy for clarithromycin-susceptible Helicobacter pylori and versus sequential therapy for clarithromycin-resistant strains.

BACKGROUND: Using quadruple clarithromycin-containing regimens for Helicobacter pylori eradication is controversial with high rates of macrolide resistance. AIM: To evaluate antibiotic resistance rates and the efficacy of empirical and tailored nonbismuth quadruple (concomitant) therapy in a setting with cure rates <80% for triple and sequential therapies. METHODS: 209 consecutive naive H. pylori-positive patients without susceptibility testing were empirically treated with 10-day concomitant therapy (proton pump inhibitors (PPI), amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg; all drugs b.i.d.). Simultaneously, 89 patients with positive H. pylori culture were randomized to receive triple versus concomitant therapy for clarithromycin-susceptible H. pylori, and sequential versus concomitant therapy for clarithromycin-resistant strains. Eradication was confirmed with ¹³C-urea breath test or histology 8 weeks after completion of treatment. RESULTS: Per-protocol (PP) and intention-to-treat eradication rates after empirical concomitant therapy without susceptibility testing were 89% (95%CI:84-93%) and 87% (83-92%). Antibiotic resistance rates were: clarithromycin, 20%; metronidazole, 34%; and both clarithromycin and metronidazole, 10%. Regarding clarithromycin-susceptible H. pylori, concomitant therapy was significantly better than triple therapy by per protocol [92% (82-100%) vs 74% (58-91%), p = 0.05] and by intention to treat [92% (82-100%) vs 70% (57-90%), p = 0.02]. As for antibiotic-resistant strains, eradication rates for concomitant and sequential therapies were 100% (5/5) vs 75% (3/4), for clarithromycin-resistant/metronidazole-susceptible strains and 75% (3/4) vs 60% (3/5) for dual-resistant strains. CONCLUSIONS: Empirical 10-day concomitant therapy achieves good eradication rates, close to 90%, in settings with multiresistant H. pylori strains. Tailored concomitant therapy is significantly superior to triple therapy for clarithromycin-susceptible H. pylori and at least as effective as sequential therapy for resistant strains.

Nonanesthesiologist-administered propofol versus midazolam and propofol, titrated to moderate sedation, for colonoscopy: a randomized controlled trial.

BACKGROUND: Nonanesthesiologist-administered propofol (NAAP) is controversial due to deep sedation concerns. AIM: The purpose of this study was to evaluate the feasibility of moderate sedation with two different NAAP regimens for colonoscopy. METHODS: This was a double-blinded, randomised, placebo-controlled trial allocating 135 consecutive outpatients to placebo (group P) or midazolam 2 mg (group M+P) before NAAP targeted to moderate sedation. Depth of sedation every 2 min throughout the procedure, propofol doses, recovery times, complications and patient and endoscopist satisfaction were measured. RESULTS: A total of 84 % of assessments of the depth of sedation were moderate. Mean induction (76 [40-150] vs. 53 [30-90]) and total propofol doses (mg) (136 [60-270] vs. 104 [50-190]) were significantly higher for group P (p < 0.001). However, deep sedation was significantly more prevalent in group M+P in minutes 4 (16 vs. 1 %, p = 0.05), 6 (20 vs. 3.5 %, p = 0.046) and 8 (17 vs. 1.8 %, p = 0.06) of the procedure, coinciding with midazolam peak action. From minute 8 on, moderate sedation was significantly deeper for M+P (p = 0.002). Early recovery time (6.8 min vs. 5.2, p = 0.007), but not discharge time (10.4 min vs. 9.8, p = 0.5), was longer for M+P. Pain perception (P 1.03 vs. M+P 0.3, p = 0.009) and patient satisfaction scores (P 9.4 vs. M+P 9.8, p = 0.047) were better for M+P. No major complications occurred. CONCLUSIONS: Moderate sedation was feasible with both NAAP regimens. Drug synergy in the midazolam plus propofol sedation regimen promotes a deeper and longer moderate sedation, improving patient satisfaction rates but prolonging early recovery time (Clinical Trials gov NCT01428882).

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn's Disease Patients: The SUSTAIN Study.

BACKGROUND: Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn's disease (CD) patients in real-world clinical practice. METHODS: A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. RESULTS: A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). CONCLUSIONS: Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice.

This large retrospective study demonstrated the short- and long-term effectiveness and safety of ustekinumab in patients with Crohn's disease in real-world clinical practice, including those with refractory disease.

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn's Disease Patients on Ustekinumab.

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index ≤ 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission.

[Octreotide long acting release for severe obscure gastrointestinal haemorrhage in elderly patients with serious comorbidities]. / Octreótido long acting release para la hemorragia digestiva en pacientes de edad avanzada con comorbilidad.

BACKGROUND AND OBJECTIVE: Octreotide LAR has shown preliminary promising results in the treatment of recurrent obscure gastrointestinal haemorrhage. PATIENTS AND METHODS: Eleven patients with severe comorbidities were treated with continuous octreotide LAR 20mg once a month. No changes were performed in concomitant drugs. Haemoglobin levels, blood transfusions, hospital admissions and adverse effects were recorded every three months. RESULTS: Median age and follow-up were 74 yr (65-86) and 15 months (5-48). Five patients were on acenocoumarol therapy and other five on antiplatelet drugs. Eight patients (72%) had diffuse small bowel angiodysplasia and 4 patients died during follow-up. Only two patients (18%) remained free of transfusions but it resulted for the first year in an outstanding decrease in the need of red cell packets (14 (9-49) vs 4 (0-9), p=0,002) and in admission days related to gastrointestinal bleeding (27 (10-99) vs 7(0-23), p=0,001). No side effects were reported. CONCLUSION: Octreotide LAR is an effective, safe and comfortable palliative therapy for severe obscure gastrointestinal bleeding. Medical resources saving and improved quality of life may warrant its use irrespective of comorbidities or life expectancy.

Prevalence of Malnutrition and Nutritional Characteristics of Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: This study sought to determine the prevalence of malnutrition in patients with inflammatory bowel disease, to analyse the dietary beliefs and behaviours of these patients, to study their body composition, to evaluate their muscular strength and to identify the factors associated with malnutrition in these patients. METHODS: This was a prospective, multicentre study. Crohn's disease and ulcerative colitis patients from 30 Spanish centres, from the outpatient clinics, were included. A questionnaire of 11 items was applied to obtain data from patients' dietary behaviour and beliefs. Patients who accepted were evaluated to assess their nutritional status using Subjective Global Assessment and body mass index. Body composition was evaluated through bioelectrical impedance. RESULTS: A total of 1271 patients were included [51% women, median age 45 years, 60% Crohn's disease]. Of these, 333 patients underwent the nutritional evaluation. A total of 77% of patients declared that they avoided some foods to prevent disease relapse. Eighty-six per cent of patients avoided some foods when they had disease activity because of fear of worsening the flare. Sixty-seven per cent of patients modified their dietary habits after disease diagnosis. The prevalence of malnutrition was 16% [95% confidence interval = 12-20%]. In the multivariate analysis, history of abdominal surgery, active disease and avoidance of some foods during flares were associated with higher risk of malnutrition. CONCLUSIONS: The prevalence of malnutrition in inflammatory bowel disease patients was high. We identified some predictive factors of malnutrition. Most of the patients had self-imposed food restrictions, based on their beliefs.