Switching from intravenous to subcutaneous infliximab and vedolizumab in patients with inflammatory bowel disease: impact on trough levels, day hospital visits, and medical expenses.

OBJECTIVE: Subcutaneous (SC) infliximab (IFX) and vedolizumab (VDZ) have recently become available. We aimed to examine the impact of switching from intravenous (IV) to SC IFX and VDZ in patients with inflammatory bowel disease (IBD) on costs, the day hospital burden, trough levels, and clinical outcomes. METHODS: Our study comprised the cohort of IBD patients receiving IV IFX or VDZ at our hospital in 2022. We evaluated costs, day hospital visits, trough levels, biochemical markers, relapse rates, and self-report outcomes until Jun 30th 2023. RESULTS: Of 114 patients, 18 continued IV therapy, 80 were switched to SC therapy, and 16 were inductions. Eighty-eight (90%) remained in steroid-free remission with no difference between the IV or SC groups. The mean IFX trough level changed from 8.2 ± 4.5 µg/ml to 14.5 ± 5.9 µg/ml, p < 0.001, and the VDZ trough level from 14.7 ± 7.1 mg/ml to 26.5 ± 13.8 mg/ml, p < 0.001. The average yearly costs of infusions and injections per patient were 2 580 € and 7 482 € for IFX and 15 990 € and 13 101 € for VDZ. The annual reduction of day hospital visits was 6,9 per patient. CONCLUSIONS: IV and SC IFX and VDZ are equally effective in maintaining remission in IBD, but SC administration reduces day hospital visits and results in higher trough levels. SC VDZ is less and SC IFX more expensive than IV therapy. Further studies are needed to assess optimal dosing and separate trough levels for SC therapy.

Tofacitinib real-world experience in ulcerative colitis in Finland (FinTofUC): a retrospective non-interventional multicenter patient chart data study.

OBJECTIVES: The aim was to define the effectiveness of tofacitinib and to characterize the patient population receiving tofacitinib in a real-world cohort clinical setting for ulcerative colitis (UC) in Finland. METHODS: This is a retrospective non-interventional multicenter patient chart data study conducted in 23 Finnish Inflammatory Bowel Disease (IBD) centers. Baseline demographic and clinical data, clinical remission, steroid-free remission rate and time to tofacitinib discontinuation, colectomy or UC-related hospitalization were studied. RESULTS: The study included 252 UC patients of which 69% were male. Most patients had extensive disease (71%) and were bio-experienced (81%). Tofacitinib demonstrated positive treatment outcomes with clinical response, clinical remission, and steroid-free clinical remission at one year in 33%, 34% and 31% of patients, respectively. Moreover, 64% of patients in pMayo remission at week 16 from the start of tofacitinib were still in remission at one year. Only no or mild disease activity compared to moderate activity at baseline was associated with a higher probability of achieving remission according to pMayo at six months, p = .008. Hospitalizations and/or colectomies during the study period (before treatment discontinuation/end of follow-up) were low (n = 24), with less than 5 colectomies. CONCLUSIONS: In this real-world cohort, including a majority of bio-experienced UC patients, tofacitinib was effective in achieving steroid-free clinical remission in a third of the population at one year. A majority of patients in remission at week 16 were also in remission at one year. Results are in line with earlier published real-world studies. Registration: ClinicalTrials.gov NCT05082428.

Characterization of inflammatory bowel disease management by vedolizumab and concomitant treatments in real-life clinical practice.

Limited data is available on vedolizumab combination therapies in real-world clinical practice. Here, we evaluated the concomitant corticosteroid, immunosuppressive, and 5-aminosalicylic acid utilization of inflammatory bowel disease (IBD) patients treated with vedolizumab in a nationwide, retrospective, non-interventional, multi-centre chart review study. All adult patients from 27 Finnish gastroenterology centres with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) who had at least one vedolizumab infusion since it's availability in Finland were included in the study. Data were collected from medical charts at baseline (vedolizumab treatment initiation), week 14, and month 6. The majority of patients who used corticosteroids at the baseline and persisted on vedolizumab treatment for 6 months were taken off corticosteroid treatment by the 6-month time point (CD, 54.5%; UC, 69.8%). Modest corticosteroid dose reductions were observed among treatment persistent CD patients from the baseline until month 6. Corticosteroid users had less vedolizumab discontinuations due to primary ineffectiveness and more discontinuations due to adverse events than patients not using corticosteroids. Vedolizumab may have a corticosteroid sparing effect in real-world clinical practice. Concomitant corticosteroid use may lead to a lower rate of vedolizumab discontinuation due to primary ineffectiveness, but a higher discontinuation rate due to adverse events.

High treatment persistence rate and significant endoscopic healing among real-life patients treated with vedolizumab - a Finnish Nationwide Inflammatory Bowel Disease Cohort Study (FINVEDO).

OBJECTIVES: The efficacy and tolerability of vedolizumab in the treatment of inflammatory bowel diseases (IBD) has been demonstrated in an extensive GEMINI clinical trial programme. Clinical trials represent highly selected patient populations and, therefore, it is important to demonstrate effectiveness in real-life clinical practice. We set out to assess real-world treatment outcomes of vedolizumab in a nationwide cohort of treatment refractory Finnish Crohn's disease (CD) and ulcerative colitis (UC) patients. METHODS: This was a nationwide, retrospective, non-interventional, multi-centre chart review study. All adult patients from 27 Finnish gastroenterology centers with a diagnosis of UC or CD who had at least one vedolizumab infusion since the availability of the product in Finland, were included in the study. Data were collected retrospectively from medical charts at baseline, week 14, and month 6. The primary outcome measure was treatment persistence 24 weeks post-vedolizumab initiation. RESULTS: A total of 247 patients were included (108 CD, 139 UC). A total of 75.0% (n = 81) of all CD patients and 66.2% (n = 92) of all UC patients, were persistent on vedolizumab therapy for 6 months post treatment initiation. At month 6, 41.8% (28/67) of the treatment persistent CD patients and 73.3% (63/86) of the treatment persistent UC patients achieved clinical remission. Significant improvement in endoscopic scores were observed among treatment persistent patients (CD, n = 17, ΔSES-CD=-5.5, p = .008; UC, n = 26, ΔMayo endoscopic score =-0.5, p = .003) at month 6. CONCLUSIONS: Vedolizumab provides an effective and well-tolerated treatment option in real-world clinical practice even among treatment refractory IBD patients.

Help from habit reversal for supragastric belching.

Supragastric belching differs from common gastric belching. It can be detected by 24-hour intra-esophageal impedance monitoring. Belching is seldom the only symptom: reflux symptom is present in 95% and dysphagia in 65% of the patients. In supragastric belching, the air does not come from the stomach but instead from the esophagus. Belching is caused by the patient him/herself swallowing air into the esophagus. This voluntary but unconscious symptom is treated by therapy in which explaining the mechanism of belching for the patient and learning of correct diaphragmatic breathing technique play a central role. Habit reversal is utilized for teaching the patient to react correctly to preemptive symptoms.

[Autonomic neuropathy--a problem of the circulatory system and digestive tract]. / Autonominen neuropatia--verenkiertoelimistön ja ruoansulatuskanavan ongelma.

An autonomic disorder of the circulatory system becomes manifest as aberrant heart rate variability and baroreflex sensitivity already years before progressing into symptomatic disease, in which case the condition is no longer curable. Diagnosis is based on tests of autonomic nervous system function. The main thing in the treatment is management of risk factors of cardiovascular diseases in addition to enhanced glucose homeostasis. Autonomic neuropathy may also affect the digestive tract and be accompanied by esophageal motility disorder, gastroparesis, diarrhea, constipation or fecal incontinence. It is essential in the diagnosis to exclude other diseases of the digestive tract.

Behavioral therapy is superior to follow-up without intervention in patients with supragastric belching-A randomized study.

BACKGROUND: Behavioral therapy (BT) has been proven effective in the treatment of supragastric belching (SGB) in open studies. The aim was to compare BT to follow-up without intervention in patients with SGB in a randomized study. METHODS: Forty-two patients were randomized to receive 5 sessions of BT, comprising diaphragmatic breathing exercises, or to follow-up without intervention. Patients were evaluated at 6 months, at which point the control group was also offered BT and evaluated after another 6 months. The frequency and intensity of belching and mental well-being were evaluated with a visual analog scale (VAS). Depression, anxiety, and health-related quality of life (HRQoL) were evaluated with four questionnaires: BDI, BAI, 15D, and RAND-36. KEY RESULTS: The frequency and intensity of SGB were significantly lower in the therapy group (n = 19) than in the control group (n = 18) at the 6-month control (p < 0.001). When all patients (n = 36) were evaluated 6 months after BT, in addition to relief in the frequency and intensity of belching (p < 0.001), mental well-being had also improved (p < 0.05). Of all 36 patients, 27(75%) responded to BT. Depression scores were lower after therapy (p < 0.05). Only minor changes occurred in anxiety and HRQoL. CONCLUSIONS AND INFERENCES: Behavioral therapy is superior to follow-up without intervention in patients with SGB in reducing belching and depression; it also improves mental well-being but has only a modest effect on anxiety and HRQoL.

Randomised clinical trial: faecal microbiota transplantation versus autologous placebo administered via colonoscopy in irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) has been associated with microbial dysbiosis. AIM: To investigate the efficacy of faecal microbiota transplantation (FMT) in the treatment of IBS. METHODS: Forty-nine IBS patients were randomised to receive autologous or allogenic FMT via colonoscopy. The primary endpoint was a sustained, minimum of 50-point, reduction in the IBS Symptom Severity Score. The secondary outcomes were levels of anxiety and depression, changes in quality of life, gut microbiota and faecal water content as assessed with validated questionnaires, intestinal microbiota composition and stool dry weight. RESULTS: The primary endpoint was not achieved in either group. However, there was a transient reduction in the mean IBS Symptom Severity Score in the FMT group at 12 weeks after treatment as compared to baseline (P = 0.01). The groups did not differ in the number of patients achieving clinical response at 12 weeks. In the FMT-treated patients, microbial composition had changed to resemble that of the donor and the stool water content decreased significantly compared to baseline. The depression score decreased in patients with a reduction in IBS symptoms after FMT, but not in those placebo-treated patients who experienced a reduction in IBS symptoms. CONCLUSIONS: FMT provided only a transient relief of symptoms, although it induced a sustained alteration in the microbiota of IBS patients. Therefore, FMT delivered by a single infusion via colonoscopy cannot be recommended as a treatment for IBS in clinical practice. ClinicalTrials.Org, Trial registration number: NCT03561519.

Does fecal calprotectin predict short-term relapse after stopping TNFα-blocking agents in inflammatory bowel disease patients in deep remission?

BACKGROUND AND AIMS: This prospective multicenter study examined whether elevated fecal calprotec tin (FC) concentrations after stopping TNFα-blocking therapy can predict clinical or endoscopic relapse. In addition, we evaluated the impact of histological remission on the relapse risk. METHODS: We enrolled inflammatory bowel disease (IBD) patients who were in clinical, endoscopic, and FC-based (< 100 µg/g) remission after a minimum 11 months of TNFα-blocking therapy. The patients were followed-up for 12 months after the discontinuation of TNFα-blocking therapy. FC was collected monthly for the first 6 months and thereafter every second month. Ileocolonoscopy was performed at inclusion, at 4 months, at the study end, and at the time of clinical relapse. RESULTS: Of 52 enrolled patients, 49 (16 Crohn's disease, 33 ulcerative colitis/IBD unclassified) provided the stool samples requested and comprised the study group. During the follow-up, 15/49 (31%) relapsed, whereas 34 (69%) remained in remission. Patients relapsing showed constantly elevated FC levels for a median of 94 (13-317) days before the relapse. Significant increase in median FC levels was seen 2 (p = 0.0014), 4 (p = 0.0056), and 6 (p = 0.0029) months before endoscopic relapse. Constantly normal FC concentrations during the follow-up were highly predictive for clinical and endoscopic remission. Normal FC concentrations in patients with remission were associated with histological remission. CONCLUSION: FC seems to increase and remain elevated before clinical or endoscopic relapse, suggesting that it can be used as a surrogate marker for predicting and identifying patients requiring close follow-up in clinical practice.

Outcome after discontinuation of TNFα-blocking therapy in patients with inflammatory bowel disease in deep remission.

BACKGROUND: Few data are available on the disease course in patients with inflammatory bowel disease (IBD) in deep remission after discontinuing tumor necrosis factor α (TNFα)-blocking therapy. In this prospective multicenter study, we evaluated the relapse rate, predictive factors, and the response to retreatment after discontinuation of TNFα-blocking therapy in patients with IBD in deep remission. METHODS: We recruited 52 patients (17 Crohn's disease, 30 ulcerative colitis, and 5 IBD unclassified) in clinical, endoscopic, and fecal calprotectin-based (<100 µg/g) remission after at least 1 year of TNFα-blocking therapy. Clinical and endoscopic remission and relapse were defined according to validated indices. After discontinuation of therapy, the patients were followed up with endoscopic assessment at 4 and 12 months. In the event of a clinical relapse with endoscopically active disease or minor clinical symptoms but severe endoscopic relapse, TNFα-blocking therapy was restarted. RESULTS: After a median follow-up time of 13 (range, 12-15) months, 17/51 (33%) patients relapsed (5/17 Crohn's disease, 12/34 ulcerative colitis/IBD unclassified, 1 patient lost to follow-up at 6 mo). Ten experienced clinical and endoscopic relapse, 5 clinical relapse with mild endoscopic activity, and 2 severe endoscopic relapse. No specific predictive factors were associated with the relapse. Retreatment was effective in 94% of patients. CONCLUSIONS: After cessation of TNFα-blocking therapy in patients with IBD in deep remission, up to 67% remained in clinical remission during the 12-month follow-up. Importantly, 85% of these patients sustained endoscopic remission. The response to restart of TNFα antagonists was effective and well tolerated.

Nizatidine and gastric emptying in functional dyspepsia.

In clinical practice, H2-receptor antagonists, including nizatidine, in addition to their use in the treatment of peptic ulcer and gastroesophageal reflux, are also useful in alleviating dyspeptic symptoms. Patients with functional dyspepsia show a tendency to delayed gastric emptying. Results of preliminary studies have demonstrated that nizatidine has a prokinetic effect due to its cholinergic properties. The aim of this study was to evaluate the effect of nizatidine on gastric emptying in patients with functional dyspepsia. Sixteen patients with dyspeptic symptoms referred for gastroscopy by primary care physicians were enrolled in this randomized, placebo-controlled, double-blind cross-over study. They received nizatidine 150 mg twice daily or placebo for 2 months. After a 1-month washout period, the 2-month treatment was repeated, with these patients acting as their own controls. Gastric emptying was measured by scintigraphy, and dyspeptic symptoms and quality of life were evaluated at the end of both treatment periods. Gastric emptying of solids during nizatidine therapy was prolonged (T1/2 110.1 +/- 76.7 vs. 65.6 +/- 23.2 min, P = 0.03), but nizatidine had no effect on gastric emptying of liquids. Nizatidine improved the symptom scores and seven of eight aspects of quality of life - but not significantly. In conclusion, nizatidine decreases the gastric emptying rate of solids without having a significant effect on symptoms or quality of life in functional dyspepsia.

Measuring gastric emptying: comparison of 13C-octanoic acid breath test and scintigraphy.

The aim of this study was to compare scintigraphy, the standard method, and the (13)C-octanoic acid breath test (OBT) for measuring gastric emptying. Patients with functional dyspepsia (N = 21, 8 men and 13 women; ages, 40-75) underwent standardized dynamic scintigraphy and OBT. Scintigraphic images were obtained for 90 min and breath samples for 4 hr. The gastric half-emptying time for solids (T(1/2)) was calculated by two previously described mathematical models for the OBT samples: the nonlinear least-squares method and the geometrical method. T(1/2) was significantly longer measured by OBT than by scintigraphy (167 +/- 50 min for the nonlinear least-squares method (P < 0.05) and 185+/- 52 min for the geometrical method (P < 0.005) vs. 109 +/- 74 min for scintigraphy). No correlation appeared between T(1/2) measured by scintigraphy and T(1/2) measured by OBT (r = 0.26) for nonlinear least-squares method and (r = -0.13) for geometrical method). Furthermore, the correlation between the two mathematical models appeared to be low (r = 0.15). Although OBT is simple and safe, its correlation with scintigraphy appears to be weak. The usefulness of this test for measuring gastric emptying thus requires further validation.