BACKGROUND: Proton-pump inhibitors (PPIs) are cornerstone treatments for gastro-esophageal reflux disease (GERD); however, evidence suggests that most patients exhibit partial response to PPIs, suggesting the need for novel therapies that can provide an improved and sustained increase in gastric pH. AIMS: This study aimed to determine the effect of vonoprazan, a novel, orally active small-molecule potassium-competitive acid blocker, versus esomeprazole, a PPI, in preventing heartburn symptoms over a 4-week treatment period in patients with GERD and a partial response to esomeprazole treatment. METHODS: This randomized, double-blind, proof-of-concept, phase 2 clinical trial was conducted between 2016 and 2018 at 39 sites across Europe and designed to evaluate the efficacy and safety of vonoprazan 20 mg once daily (q.d.) and 40 mg q.d. versus esomeprazole 40 mg q.d. after 1:1:1 randomization of symptomatic patients with GERD and a partial response to a healing dose of esomeprazole. RESULTS: Overall, 256 eligible patients (female, 59.4%; mean age, 52.6 years) received vonoprazan 20 mg (n = 85), vonoprazan 40 mg (n = 85), or esomeprazole 40 mg (n = 86); mean (SD) percentages of heartburn-free 24-h periods during double-blind treatment were 36.7% (33.4%), 36.5% (35.6%), and 38.4% (34.8%), respectively, with no intergroup statistical significance. Vonoprazan exposure increased proportionally from the 20-mg to 40-mg dose (mean Cmax : 23.3 ng/ml to 47.1 ng/ml, respectively). Most treatment-emergent adverse events were mild, with no deaths reported. CONCLUSIONS: No statistically significant difference in efficacy and safety was observed among treatment groups, and vonoprazan was well tolerated. The trial is registered with the National Board of Health (EudraCT: 2015-001154-14) database.
- MeSH
- dvojitá slepá metoda MeSH
- esomeprazol * terapeutické užití MeSH
- gastroezofageální reflux * farmakoterapie diagnóza MeSH
- inhibitory protonové pumpy terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- pyróza farmakoterapie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND AND AIMS: Ontamalimab, a fully-human monoclonal antibody targeting MAdCAM-1, induced remission in patients with moderate-to-severe ulcerative colitis [UC] in the TURANDOT study. We aimed to assess long-term safety, tolerability, and efficacy of ontamalimab in TURANDOT II. METHODS: TURANDOT II was a phase 2, multicentre, open-label [OL] study in patients with moderate-to-severe UC who completed TURANDOT on placebo or ontamalimab (NCT01771809). Patients were randomised to 75 mg or 225 mg ontamalimab every 4 weeks for 72 weeks [OL1]. The dosage could be increased to 225 mg from Week 8 at the investigator's discretion. All patients then received 75 mg every 4 weeks for 72 weeks [OL2], followed by 6-month safety follow-up. The primary objective was safety, measured by adverse events [AEs], serious AEs [SAEs], and AEs leading to withdrawal. Mucosal healing [MH; centrally read endoscopy] was assessed. RESULTS: Of 330 patients, 180 completed OL1; 94 escalated to 225 mg; 127 completed OL2. Overall, 36.1% experienced drug-related AEs. The most common SAE [10.0%] was worsening/ongoing UC; 5.5% of patients had serious infections, the most common being gastroenteritis [0.9%]. One death and four cancers [all unrelated to ontamalimab] occurred. No PML [progressive multifocal leukoencephalopathy]/lymphoproliferative disorders occurred. Geometric mean high-sensitivity C-reactive protein [hsCRP] and faecal calprotectin decreased across OL1 in both dose groups. The proportion of patients assigned to placebo in TURANDOT achieving MH increased from 8.8% [6/68] at baseline to 35.3% at Week 16 [24/68; non-responder imputation]. The corresponding increase in the ontamalimab group was from 23.3% [61/262] to 26.7% [70/262]. CONCLUSIONS: Ontamalimab was well tolerated up to 144 weeks in patients with moderate-to-severe UC, with good safety and efficacy.
- MeSH
- C-reaktivní protein analýza MeSH
- dospělí MeSH
- gastrointestinální endoskopie metody statistika a číselné údaje MeSH
- gastrointestinální látky aplikace a dávkování škodlivé účinky MeSH
- humanizované monoklonální protilátky * aplikace a dávkování škodlivé účinky MeSH
- imunologická odpověď na dávku MeSH
- leukocytární L1-antigenní komplex analýza MeSH
- lidé MeSH
- molekuly buněčné adheze antagonisté a inhibitory MeSH
- monitorování léčiv * metody statistika a číselné údaje MeSH
- mukoproteiny antagonisté a inhibitory MeSH
- ulcerózní kolitida * diagnóza farmakoterapie imunologie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
OBJECTIVE: To evaluate the cost-effectiveness of an inflammatory biomarker and clinical symptom directed tight control strategy (TC) compared with symptom-based clinical management (CM) in patients with Crohn's disease (CD) naïve to immunosuppressants and biologics using a UK public payer perspective. DESIGN: A regression model estimated weekly CD Activity Index (CDAI)-based transition matrices (remission: CDAI <150, moderate: CDAI ≥150 to <300, severe: CDAI ≥300 to <450, very severe: CDAI ≥450) based on the Effect of Tight Control Management on Crohn's Disease (CALM) trial. A regression predicted hospitalisations. Health utilities and costs were applied to health states. Work productivity was monetised and included in sensitivity analyses. Remission rate, CD-related hospitalisations, adalimumab injections, other direct medical costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. RESULTS: Over 48 weeks, TC was associated with a higher clinical remission (CDAI <150) rate (58.2% vs 46.8%), fewer CD-related hospitalisations (0.124 vs 0.297 events per patient) and more injections of adalimumab (40 mg sc) (mean 31.0 vs 24.7) than CM. TC was associated with 0.032 higher QALYs and £593 higher total medical costs. The ICER was £18 656 per QALY. The ICER was cost-effective in 57.9% of simulations. TC became dominant, meaning less costly but more effective, when work productivity was included. CONCLUSION: A TC strategy as used in the CALM trial is cost-effective compared with CM. Incorporating costs related to work productivity increases the economic value of TC. Cross-national inferences from this analysis should be made with caution given differences in healthcare systems. TRIAL REGISTRATION NUMBER: NCT01235689; Results.
- MeSH
- adalimumab terapeutické užití MeSH
- analýza nákladů a výnosů MeSH
- antiflogistika terapeutické užití MeSH
- biologické markery metabolismus MeSH
- C-reaktivní protein metabolismus MeSH
- Crohnova nemoc farmakoterapie metabolismus MeSH
- hospitalizace MeSH
- kvalitativně upravené roky života MeSH
- leukocytární L1-antigenní komplex metabolismus MeSH
- lidé MeSH
- určení symptomu MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Spojené království MeSH
ESGE suggests flexible endoscopic treatment over open surgical treatment as first-line therapy for patients with a symptomatic Zenker's diverticulum of any size.Weak recommendation, low quality of evidence, level of agreement 100 %.ESGE recommends that emerging treatments for Zenker's diverticulum, such as Zenker's peroral endoscopic myotomy (Z-POEM) and tunneling, be considered as experimental; these treatments should be offered in a research setting only.Strong recommendation, low quality of evidence, level of agreement 100 %.ESGE recommends against the widespread clinical use of transoral incisionless fundoplication (TIF) as an alternative to proton pump inhibitor (PPI) therapy or antireflux surgery in the treatment of gastroesophageal reflux disease (GERD), because of the lack of data on the long-term outcomes, the inferiority of TIF to fundoplication, and its modest efficacy in only highly selected patients. TIF may have a role for patients with mild GERD who are not willing to take PPIs or undergo antireflux surgery.Strong recommendation, moderate quality of evidence, level of agreement 92.8 %.ESGE recommends against the use of the Medigus ultrasonic surgical endostapler (MUSE) in clinical practice because of insufficient data showing its effectiveness and safety in patients with GERD. MUSE should be used in clinical trials only.Strong recommendation, low quality evidence, level of agreement 100 %.ESGE recommends against the use of antireflux mucosectomy (ARMS) in routine clinical practice in the treatment of GERD because of the lack of data and its potential complications.Strong recommendation, low quality evidence, level of agreement 100 %.ESGE recommends endoscopic cecostomy only after conservative management with medical therapies or retrograde lavage has failed.Strong recommendation, low quality evidence, level of agreement 93.3 %.ESGE recommends fixing the cecum to the abdominal wall at three points (using T-anchors, a double-needle suturing device, or laparoscopic fixation) to prevent leaks and infectious adverse events, whatever percutaneous endoscopic cecostomy method is used.Strong recommendation, very low quality evidence, level of agreement 86.7 %.ESGE recommends considering endoscopic decompression of the colon in patients with Ogilvie's syndrome that is not improving with conservative treatment.Strong recommendation, low quality evidence, level of agreement 93.8 %.ESGE recommends prompt endoscopic decompression if the cecal diameter is > 12 cm and if the Ogilvie's syndrome exists for a duration of longer than 4 - 6 days.Strong recommendation, low quality evidence, level of agreement 87.5 %.
ESGE recommends the use of a graded pneumatic dilation protocol in achalasia, starting with a 30-mm dilation and followed by a 35-mm dilation at a planned interval of 2 - 4 weeks, with a subsequent 40-mm dilation when there is insufficient relief, over both a single balloon dilation procedure or the use of a larger balloon from the outset.Strong recommendation, high quality of evidence, level of agreement 100 %.ESGE recommends being cautious in treating spastic motility disorders other than achalasia with peroral endoscopic myotomy (POEM).Strong recommendation, very low quality of evidence, level of agreement 87.5 %.ESGE recommends against the routine use of botulinum toxin injections to treat patients with non-achalasia hypercontractile esophageal motility disorders (Jackhammer esophagus, distal esophageal spasm). However, if, in individual patients, endoscopic injection of botulinum toxin is chosen, ESGE recommends performing injections into four quadrants of the lower esophageal sphincter and in the lower third of the esophagus.Strong recommendation, low quality of evidence, level of agreement 78.6 %.ESGE recommends that endoscopic pylorus-directed therapy should be considered only in patients with symptoms suggestive of gastroparesis in combination with objective proof of delayed gastric emptying using a validated test, and only when medical therapy has failed.Strong recommendation, very low quality of evidence, level of agreement 100 %.ESGE recommends against the use of botulinum toxin injection in the treatment of unselected patients with gastroparesis. Strong recommendation, high quality of evidence, level of agreement 92.9 %.ESGE recommends consideration of gastric peroral endoscopic myotomy (G-POEM) in carefully selected patients only, because it is an emerging procedure with limited data on effectiveness, safety, and durability. G-POEM should be performed in expert centers only, preferably in the context of a clinical trial.Strong recommendation, low quality of evidence, level of agreement 100 %.
