Safety and Effectiveness of Vedolizumab and Ustekinumab in Elderly Patients with Inflammatory Bowel Disease: A Real-Life Multicentric Cohort Study.

BACKGROUND: Data on ustekinumab and vedolizumab in the elderly inflammatory bowel disease (IBD) population are limited. The aim of the current study was to assess the safety and effectiveness of both in an elderly real-life population. METHODS: A multicentric retrospective study was performed on IBD patients who started vedolizumab or ustekinumab between 2010 and 2020. Clinical and endoscopic remission rates and (serious) adverse events (AE) were assessed. RESULTS: A total of 911 IBD patients were included, with 171 (19%) aged above 60 (111 VDZ, 60 UST). Elderly patients treated with vedolizumab or ustekinumab had an increased risk for non-IBD hospitalization (10.5% vs. 5.7%, p = 0.021) and malignancy (2.3% vs. 0.5%, p = 0.045) compared to the younger population. Corticosteroid-free clinical (50% vs. 44%; p = 0.201) and endoscopic remission rates (47.9% vs. 31%, p = 0.07) at 1 year were similar. Comparing vedolizumab to ustekinumab in the elderly population, corticosteroid-free (47.9% vs. 31%, p = 0.061) and endoscopic remission rates (66.7% vs. 64.4%, p = 0.981) were similar. Vedolizumab- and ustekinumab-treated patients had comparable infection rates (13.5% vs. 10.0%, p = 0.504), IBD flare-ups (4.5% vs. 5%, p = 1.000), the occurrence of new EIMs (13.5% vs. 10%, p = 0.504), a risk of intestinal surgery (5.4% vs. 6.7%, p = 0.742), malignancy (1.8% vs. 3.3%, p = 0.613), hospitalization (9.9% vs. 11.7%, p = 0.721), and mortality (0.9% vs. 1.7%, p = 1.000). AE risk was associated only with corticosteroid use. CONCLUSIONS: Ustekinumab and vedolizumab show comparable effectiveness and safety in the elderly IBD population. Elderly IBD patients have an increased risk for non-IBD hospitalizations and malignancy compared to the younger IBD population, with corticosteroid use as the main risk factor.

Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial.

BACKGROUND & AIMS: Fatigue is highly prevalent among patients with inflammatory bowel disease (IBD), and only limited treatment options are available. Based on the hypothetical link between low serum tryptophan concentrations and fatigue, we determined the effect of 5-hydroxytryptophan supplementation on fatigue in patients with inactive IBD. METHODS: A multicenter randomized controlled trial was performed at 13 Belgian hospitals, including 166 patients with IBD in remission but experiencing fatigue, defined by a fatigue visual analog scale (fVAS) score of ≥5. Patients were treated in a crossover manner with 100 mg oral 5-hydroxytryptophan or placebo twice daily for 2 consecutive periods of 8 weeks. The primary end point was the proportion of patients reaching a ≥20% reduction in fVAS after 8 weeks of intervention. Secondary outcomes included changes in serum tryptophan metabolites, Functional Assessment of Chronic Illness Therapy Fatigue scale, and scores for depression, anxiety, and stress. The effect of the intervention on the outcomes was evaluated by linear mixed modeling. RESULTS: During 5-hydroxytryptophan treatment, a significant increase in serum 5-hydroxytryptophan (estimated mean difference, 52.66 ng/mL; 95% confidence interval [CI], 39.34-65.98 ng/mL; P < .001) and serotonin (3.0 ng/mL; 95 CI, 1.97-4.03 ng/mL; P < .001) levels was observed compared with placebo. The proportion of patients reaching ≥20% reduction in fVAS was similar in placebo- (37.6%) and 5-hydroxytryptophan (35.6%)-treated patients (P = .830). The fVAS reduction (-0.18; 95% CI, -0.81 to 0.46; P = .581) and Functional Assessment of Chronic Illness Therapy Fatigue scale increase (0.68; 95% CI, -2.37 to 3.73; P = .660) were both comparable between 5-hydroxytryptophan and placebo treatment as well as changes in depression, anxiety, and stress scores. CONCLUSIONS: Despite a significant increase in serum 5-hydroxytryptophan and serotonin levels, oral 5-hydroxytryptophan did not modulate IBD-related fatigue better than placebo. (Trial Registration: Belgian Federal Agency for Medication and Health Products, EudraCT number: 2017-005059-10 and ClinicalTrials.gov: NCT03574948, https://clinicaltrials.gov/ct2/show/NCT03574948.).

The Impact of Vedolizumab and Ustekinumab on Articular Extra-Intestinal Manifestations in Inflammatory Bowel Disease Patients: A Real-Life Multicentre Cohort Study.

BACKGROUND AND AIMS: Extra-intestinal manifestations are frequently reported in inflammatory bowel diseases. However, data comparing the effect of vedolizumab and ustekinumab on articular extra-intestinal manifestations are limited. The aim here was to evaluate differences in new-onset and the evolution of pre-existing joint extra-intestinal manifestations during both treatments. METHODS: An international multicentre retrospective study was performed on inflammatory bowel disease patients who started vedolizumab or ustekinumab between May 2010 and December 2020. Extra-intestinal manifestations were assessed at baseline and joint extra-intestinal manifestations were evaluated throughout the 2-year follow-up. Arthropathy was defined by joint inflammation [arthritis/sacroiliitis], diagnosed by a rheumatologist, and arthralgia as articular pain without confirmed inflammation. Additionally, skin, ocular and hepatic extra-intestinal manifestations were assessed at baseline. Uni- and multivariate analyses were performed. RESULTS: In total, 911 patients [vedolizumab: 584; ustekinumab: 327] were included. Deterioration of pre-existing arthropathy and rate of new-onset arthropathy were not significantly associated with vedolizumab over ustekinumab. Arthropathy was used as reason to stop treatment in six vedolizumab and two ustekinumab patients. The odds of developing new arthralgia within 6 months was higher in patients who took vedolizumab compared to ustekinumab (adjusted odds ratio [aOR]: 2.28 [1.01-5.15], p = 0.047). However, this effect was not sustained during the 2-year follow-up (aOR: 1.35 [0.80-2.29], p = 0.259). Deterioration of pre-existing arthralgia was comparable between ustekinumab and vedolizumab-treated patients. In two vedolizumab-treated patients arthralgia was given as the reason to stop treatment. CONCLUSIONS: Vedolizumab and ustekinumab can be used safely in patients with articular extra-intestinal manifestations. Only a temporary increased risk for developing arthralgia has been observed under vedolizumab.

Gastroesophageal reflux evaluation in patients affected by chronic cough: Restech versus multichannel intraluminal impedance/pH metry.

OBJECTIVES/HYPOTHESIS: Oropharyngeal (OP) pH monitoring has been developed to detect supra-esophageal gastric reflux (SEGR). The results obtained with OP pH-metry and multichannel intraluminal impedance/pH monitoring (MII/pH) were compared. STUDY DESIGN: Diagnostic study. METHODS: Ten patients (age 46.33 ± 9.86 years) presenting with chronic coughing underwent simultaneous OP and MII/pH recording. A 2-minute interval was allowed between events detected with both techniques to be considered simultaneous. RESULTS: A total of 515 reflux episodes were recorded with MII/pH (acid: 181; weakly acid: 310; weakly alkaline: 24); 180 (35%) reached the highest impedance channel (hypo-pharynx); 74/180 (41%) were not related to a change in pH, according to the antimony electrode of the MII/pH catheter located at the upper esophageal sphincter. The OP monitoring measured 39 acid events; 17 (43.6%) were swallows according to MII, and 15 (38.5%) were not associated with MII or pH change. Only seven episodes were detected simultaneously with both techniques (1.3% for MII vs. 18% for OP; P = 0.0002). We found 49 pH-only refluxes at the pH sensor in the hypo-pharynx with MII/pH; only three (6.1%) correlated with OP reflux. Correlation in time between cough and reflux events was positive in 5/10 patients for MII (symptom index 5/10, symptom association probability 4/10), but in 0/10 patients according to OP pH metry. CONCLUSION: OP pH metry detected less reflux episodes than MII/pH; 35% of the OP events were swallows according to impedance. Time correlation between cough and reflux could not be demonstrated with OP pH metry.

Thoracoscopic findings and pharmacokinetics of inhaled fluorescein in a pig model.

BACKGROUND: Fluorescein-enhanced autofluorescence thoracoscopy (FEAT) reveals regions of abnormal fluorescence in patients with primary spontaneous pneumothorax and in normal subjects. Some of these lesions are undetectable by white light thoracoscopy and it has been hypothesized that they represent underlying pleural and/or parenchymal abnormalities. OBJECTIVES: In order to standardize and evaluate this novel technique, we developed an animal model. METHODS: Six pigs underwent thoracoscopy after the inhalation of nebulized sodium fluorescein by either volume-controlled mechanical ventilation or spontaneous ventilation. Pleural cavity and lung surface were inspected by white light thoracoscopy and FEAT during a period of 90 min. Fluorescence intensities were quantified in pleura and in blood. Regions of interest were examined postmortem for a histological assessment of the lesions. RESULTS: FEAT lesions were observed in all animals, with a maximum intensity of the lesions 20-30 min after the onset of fluorescein administration. The plasma concentrations of sodium fluorescein reached a maximum after approximately 20 min. The microscopic findings suggest that fluorescein accumulates in the subpleural space of better ventilated lung areas. CONCLUSIONS: This is the first animal model using FEAT. Valuable information has been gathered but further investigations are required to explain the phenomena observed in humans and pigs.