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ABSTRACT: Hemophagocytic lymphohistiocytosis (HLH) comprises a severe hyperinflammatory phenotype driven by the overproduction of cytokines, many of which signal via the JAK/STAT pathway. Indeed, the JAK1/2 inhibitor ruxolitinib has demonstrated efficacy in preclinical studies and early-phase clinical trials in HLH. Nevertheless, concerns remain for ruxolitinib-induced cytopenias, which are postulated to result from the blockade of JAK2-dependent hematopoietic growth factors. To explore the therapeutic effects of selective JAK inhibition in mouse models of HLH, we carried out studies incorporating the JAK1 inhibitor itacitinib, JAK2 inhibitor fedratinib, and JAK1/2 inhibitor ruxolitinib. All 3 drugs were well-tolerated and at the doses tested, they suppressed interferon-gamma (IFN-γ)-induced STAT1 phosphorylation in vitro and in vivo. Itacitinib, but not fedratinib, significantly improved survival and clinical scores in CpG-induced secondary HLH. Conversely, in primary HLH, in which perforin-deficient (Prf1-/-) mice are infected with lymphocytic choriomeningitis virus (LCMV), itacitinib, and fedratinib performed suboptimally. Ruxolitinib demonstrated excellent clinical efficacy in both HLH models. RNA-sequencing of splenocytes from LCMV-infected Prf1-/- mice revealed that itacitinib targeted inflammatory and metabolic pathway genes in CD8 T cells, whereas fedratinib targeted genes regulating cell proliferation and metabolism. In monocytes, neither drug conferred major transcriptional impacts. Consistent with its superior clinical effects, ruxolitinib exerted the greatest transcriptional changes in CD8 T cells and monocytes, targeting more genes across several biologic pathways, most notably JAK-dependent proinflammatory signaling. We conclude that JAK1 inhibition is sufficient to curtail CpG-induced disease, but combined inhibition of JAK1 and JAK2 is needed to best control LCMV-induced immunopathology.
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Modelos Animales de Enfermedad , Linfohistiocitosis Hemofagocítica , Nitrilos , Pirazoles , Pirimidinas , Animales , Pirimidinas/farmacología , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Linfohistiocitosis Hemofagocítica/inducido químicamente , Linfohistiocitosis Hemofagocítica/patología , Pirazoles/farmacología , Pirazoles/uso terapéutico , Ratones , Janus Quinasa 1/antagonistas & inhibidores , Janus Quinasa 1/metabolismo , Janus Quinasa 1/genética , Pirroles/farmacología , Pirroles/uso terapéutico , Janus Quinasa 2/antagonistas & inhibidores , Janus Quinasa 2/genética , Janus Quinasa 2/metabolismo , Ratones Endogámicos C57BL , Sulfonamidas/farmacología , Sulfonamidas/uso terapéutico , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT1/genética , Inhibidores de las Cinasas Janus/farmacología , Inhibidores de las Cinasas Janus/uso terapéutico , Piperidinas/farmacología , Humanos , Bencenosulfonamidas , Hidrocarburos Aromáticos con Puentes , PirrolidinasRESUMEN
BACKGROUND: Chronic hand eczema is a fluctuating, inflammatory, pruritic, often painful disease of hands and wrists that strongly impacts quality of life and occupational capabilities of patients. The aim of phase 3 DELTA 1 and DELTA 2 was to assess the efficacy and safety of twice-daily applications of the topical pan-Janus kinase inhibitor delgocitinib cream 20 mg/g versus cream vehicle in adults with moderate to severe chronic hand eczema. METHODS: Both trials were randomised, double-blinded, and vehicle-controlled, with DELTA 1 being conducted at 53 trial centres in Canada, France, Germany, Italy, Poland, and the UK and DELTA 2 at 50 trial centres in Belgium, Canada, Denmark, Germany, the Netherlands, Poland, and Spain. Adults (aged ≥18 years) with moderate to severe chronic hand eczema were randomly assigned 2:1 to twice-daily delgocitinib cream 20 mg/g or cream vehicle for 16 weeks. The primary endpoint was Investigator's Global Assessment for Chronic Hand Eczema (IGA-CHE) treatment success at week 16, defined as IGA-CHE score of 0 (clear) or 1 (almost clear, defined as only barely perceptible erythema). Efficacy and safety were assessed in all patients who were exposed to trial treatment. These trials are registered with ClinicalTrials.gov, NCT04871711 and NCT04872101. FINDINGS: Between May 10, 2021, and Oct 31, 2022, 487 patients (181 male and 306 female) were enrolled in DELTA 1; between May 25, 2021, and Jan 6, 2023, 473 patients (161 male and 312 female) were enrolled in DELTA 2. 325 patients in DELTA 1 and 314 in DELTA 2 were assigned to delgocitinib cream; 162 patients in DELTA 1 and 159 in DELTA 2 were assigned to cream vehicle. At week 16, a greater proportion of delgocitinib-treated patients versus cream vehicle patients had IGA-CHE treatment success (64 [20%] of 325 vs 16 [10%] of 162 in DELTA 1 and 91 [29%] of 313 vs 11 [7%] of 159 in DELTA 2; both trials p≤0·0055). The proportion of patients who reported adverse events was similar with delgocitinib (147 [45%] of 325 in DELTA 1 and 143 [46%] of 313 in DELTA 2) and the cream vehicle (82 [51%] of 162 in DELTA 1 and 71 [45%] of 159 in DELTA 2). Most frequent adverse events occurring in at least 2% of patients were similar in both treatment groups and included COVID-19 and nasopharyngitis. INTERPRETATION: Overall, delgocitinib cream showed superior efficacy versus cream vehicle and was well tolerated over 16 weeks. These results support the clinical benefit of delgocitinib cream as a potential treatment option for patients with moderate to severe chronic hand eczema, who are unable to adequately control their disease with basic skin care practices and topical corticosteroids. FUNDING: LEO Pharma.
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Eccema , Dermatosis de la Mano , Pirroles , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Crónica , Método Doble Ciego , Eccema/tratamiento farmacológico , Dermatosis de la Mano/tratamiento farmacológico , Pirroles/uso terapéutico , Índice de Severidad de la Enfermedad , Crema para la Piel , Resultado del TratamientoRESUMEN
Rationale: Pharmacological improvement of cystic fibrosis transmembrane conductance regulator (CFTR) function with elexacaftor/tezacaftor/ivacaftor (ETI) provides unprecedented improvements in lung function and other clinical outcomes in patients with cystic fibrosis (CF). However, ETI effects on impaired mucosal homeostasis and host defense at the molecular and cellular levels in the airways of patients with CF remain unknown. Objectives: To investigate effects of ETI on the transcriptome of nasal epithelial and immune cells from children with CF at the single-cell level. Methods: Nasal swabs from 13 children with CF and at least one F508del allele aged 6 to 11 years were collected at baseline and 3 months after initiation of ETI, subjected to single-cell RNA sequencing, and compared with swabs from 12 age-matched healthy children. Measurements and Main Results: Proportions of CFTR-positive cells were decreased in epithelial basal, club, and goblet cells, but not in ionocytes, from children with CF at baseline and were restored by ETI therapy to nearly healthy levels. Single-cell transcriptomics revealed an impaired IFN signaling and reduced expression of major histocompatibility complex classes I and II encoding genes in epithelial cells of children with CF at baseline, which was partially restored by ETI. In addition, ETI therapy markedly reduced the inflammatory phenotype of immune cells, particularly of neutrophils and macrophages. Conclusions: Pharmacological improvement of CFTR function improves innate mucosal immunity and reduces immune cell inflammatory responses in the upper airways of children with CF at the single-cell level, highlighting the potential to restore epithelial homeostasis and host defense in CF airways by early initiation of ETI therapy.
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Aminofenoles , Benzodioxoles , Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Homeostasis , Humanos , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/inmunología , Fibrosis Quística/fisiopatología , Niño , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Femenino , Masculino , Benzodioxoles/uso terapéutico , Benzodioxoles/farmacología , Aminofenoles/uso terapéutico , Aminofenoles/farmacología , Quinolonas/uso terapéutico , Quinolonas/farmacología , Indoles/uso terapéutico , Indoles/farmacología , Combinación de Medicamentos , Quinolinas/uso terapéutico , Quinolinas/farmacología , Pirazoles/uso terapéutico , Pirazoles/farmacología , Pirroles/uso terapéutico , Pirroles/farmacología , Mucosa Nasal/inmunología , Piridinas/uso terapéutico , Piridinas/farmacologíaRESUMEN
SOURCE CITATION: Zhuang Q, Chen S, Zhou X, et al. Comparative efficacy of P-CAB vs proton pump inhibitors for grade C/D esophagitis: a systematic review and network meta-analysis. Am J Gastroenterol. 2024;119:803-813. 38345252.
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Inhibidores de la Bomba de Protones , Pirroles , Sulfonamidas , Humanos , Esofagitis/tratamiento farmacológico , Esofagitis Péptica/tratamiento farmacológico , Inhibidores de la Bomba de Protones/uso terapéutico , Pirroles/uso terapéutico , Sulfonamidas/uso terapéutico , Revisiones Sistemáticas como Asunto , Metaanálisis como AsuntoRESUMEN
BACKGROUND AND AIMS: This study aimed to evaluate the efficacy and safety of vonoprazan and tetracycline (VT) dual therapy as first-line treatment for Helicobacter pylori infection in patients with penicillin allergy. METHODS: In this randomised controlled trial, treatment-naïve adults with H. pylori infection and penicillin allergy were randomised 1:1 to receive either open-label VT dual therapy (vonoprazan 20 mg two times per day+tetracycline 500 mg three times a day) or bismuth quadruple therapy (BQT; lansoprazole 30 mg two times per day+colloidal bismuth 150 mg three times a day+tetracycline 500 mg three times a day+metronidazole 400 mg three times a day) for 14 days. The primary outcome was non-inferiority in eradication rates in the VT dual group compared with the BQT group. Secondary outcomes included assessing adverse effects. RESULTS: 300 patients were randomised. The eradication rates in the VT group and the BQT group were: 92.0% (138/150, 95% CI 86.1% to 95.6%) and 89.3% (134/150, 95% CI 83.0% to 93.6%) in intention-to-treat analysis (difference 2.7%; 95% CI -4.6% to 10.0%; non-inferiority p=0.000); 94.5% (138/146, 95% CI 89.1% to 97.4%) and 93.1% (134/144, 95% CI 87.3% to 96.4%) in modiï¬ed intention-to-treat analysis (difference 1.5%; 95% CI -4.9% to 8.0%; non-inferiority p=0.001); 95.1% (135/142, 95% CI 89.7% to 97.8%) and 97.7% (128/131, 95% CI 92.9% to 99.4%) in per-protocol analysis (difference 2.6%; 95% CI -2.9% to 8.3%; non-inferiority p=0.000). The treatment-emergent adverse events (TEAEs) were significantly lower in the VT group (14.0% vs 48.0%, p=0.000), with fewer treatment discontinuations due to TEAEs (2.0% vs 8.7%, p=0.010). CONCLUSIONS: VT dual therapy demonstrated efficacy and safety as a first-line treatment for H. pylori infection in the penicillin-allergic population, with comparable efficacy and a lower incidence of TEAEs compared with traditional BQT. TRIAL REGISTRATION NUMBER: ChiCTR2300074693.
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Antibacterianos , Hipersensibilidad a las Drogas , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Penicilinas , Pirroles , Sulfonamidas , Tetraciclina , Humanos , Sulfonamidas/efectos adversos , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Hipersensibilidad a las Drogas/etiología , Tetraciclina/uso terapéutico , Tetraciclina/efectos adversos , Tetraciclina/administración & dosificación , Penicilinas/efectos adversos , Penicilinas/uso terapéutico , Pirroles/efectos adversos , Pirroles/uso terapéutico , Pirroles/administración & dosificación , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Adulto , Bismuto/uso terapéutico , Bismuto/efectos adversos , Bismuto/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéutico , Resultado del Tratamiento , Anciano , Metronidazol/efectos adversos , Metronidazol/uso terapéutico , Metronidazol/administración & dosificación , Lansoprazol/uso terapéutico , Lansoprazol/administración & dosificación , Lansoprazol/efectos adversosRESUMEN
Pancreatic cancer is highly lethal. New diagnostic and treatment modalities are desperately needed. We report here that an expanded porphyrin, cyclo[8]pyrrole (CP), with a high extinction coefficient (89.16 L/g·cm) within the second near-infrared window (NIR-II), may be formulated with an αvß3-specific targeting peptide, cyclic-Arg-Gly-Asp (cRGD), to form cRGD-CP nanoparticles (cRGD-CPNPs) with promising NIR-II photothermal (PT) therapeutic and photoacoustic (PA) imaging properties. Studies with a ring-array PA tomography system, coupled with analysis of control nanoparticles lacking a targeting element (CPNPs), revealed that cRGD conjugation promoted the delivery of the NPs through abnormal vessels around the tumor to the solid tumor core. This proved true in both subcutaneous and orthotopic pancreatic tumor mice models, as confirmed by immunofluorescent studies. In combination with NIR-II laser photoirradiation, the cRGD-CPNPs provided near-baseline tumor growth inhibition through PTT both in vitro and in vivo. Notably, the combination of the present cRGD-CPNPs and photoirradiation was found to inhibit intra-abdominal metastases in an orthotopic pancreatic tumor mouse model. The cRGD-CPNPs also displayed good biosafety profiles, as inferred from PA tomography, blood analyses, and H&E staining. They thus appear promising for use in combined PA imaging and PT therapeutic treatment of pancreatic cancer.
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Nanopartículas , Neoplasias Pancreáticas , Técnicas Fotoacústicas , Animales , Ratones , Pirroles/uso terapéutico , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/terapia , Nanopartículas/química , Tomografía Computarizada por Rayos X , Técnicas Fotoacústicas/métodos , Línea Celular Tumoral , FototerapiaRESUMEN
BACKGROUND: Atogepant is an oral, small-molecule, calcitonin gene-related peptide receptor antagonist that is being investigated for the preventive treatment of migraine. METHODS: In a phase 3, double-blind trial, we randomly assigned adults with 4 to 14 migraine days per month in a 1:1:1:1 ratio to receive a once-daily dose of oral atogepant (10 mg, 30 mg, or 60 mg) or placebo for 12 weeks. The primary end point was the change from baseline in the mean number of migraine days per month across the 12 weeks. Secondary end points included headache days per month, a reduction from baseline of at least 50% in the 3-month average of migraine days per month, quality of life, and scores on the Activity Impairment in Migraine-Diary (AIM-D). RESULTS: A total of 2270 participants were screened, 910 were enrolled, and 873 were included in the efficacy analysis; 214 were assigned to the 10-mg atogepant group, 223 to the 30-mg atogepant group, 222 to the 60-mg atogepant group, and 214 to the placebo group. The mean number of migraine days per month at baseline ranged from 7.5 to 7.9 in the four groups. The changes from baseline across 12 weeks were -3.7 days with 10-mg atogepant, -3.9 days with 30-mg atogepant, -4.2 days with 60-mg atogepant, and -2.5 days with placebo. The mean differences from placebo in the change from baseline were -1.2 days with 10-mg atogepant (95% confidence interval [CI], -1.8 to -0.6), -1.4 days with 30-mg atogepant (95% CI, -1.9 to -0.8), and -1.7 days with 60-mg atogepant (95% CI, -2.3 to -1.2) (P<0.001 for all comparisons with placebo). Results for the secondary end points favored atogepant over placebo with the exceptions of the AIM-D Performance of Daily Activities score and the AIM-D Physical Impairment score for the 10-mg dose. The most common adverse events were constipation (6.9 to 7.7% across atogepant doses) and nausea (4.4 to 6.1% across atogepant doses). Serious adverse events included one case each of asthma and optic neuritis in the 10-mg atogepant group. CONCLUSIONS: Oral atogepant once daily was effective in reducing the number of migraine days and headache days over a period of 12 weeks. Adverse events included constipation and nausea. Longer and larger trials are needed to determine the effect and safety of atogepant for migraine prevention. (Funded by Allergan; ADVANCE ClinicalTrials.gov number, NCT03777059.).
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Antagonistas del Receptor Peptídico Relacionado con el Gen de la Calcitonina/administración & dosificación , Trastornos Migrañosos/prevención & control , Piperidinas/administración & dosificación , Piridinas/administración & dosificación , Pirroles/administración & dosificación , Compuestos de Espiro/administración & dosificación , Adolescente , Adulto , Anciano , Antagonistas del Receptor Peptídico Relacionado con el Gen de la Calcitonina/efectos adversos , Antagonistas del Receptor Peptídico Relacionado con el Gen de la Calcitonina/uso terapéutico , Estreñimiento/inducido químicamente , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Piperidinas/efectos adversos , Piperidinas/uso terapéutico , Piridinas/efectos adversos , Piridinas/uso terapéutico , Pirroles/efectos adversos , Pirroles/uso terapéutico , Compuestos de Espiro/efectos adversos , Compuestos de Espiro/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND & AIMS: Potassium-competitive acid blockers (PCABs) have been increasingly used to treat upper gastrointestinal disorders, replacing proton pump inhibitors (PPIs). Whereas PPIs are associated with an increased risk of gastric cancer (GC) after Helicobacter pylori (Hp) eradication, it is uncertain whether PCABs carry the same risk. METHODS: Using a population-based claims database in Japan, we identified patients who were prescribed a clarithromycin-based first regimen of Hp eradication between 2015 and 2018. Patients who failed this regimen and those diagnosed with GC before or within 1 year after Hp eradication were excluded. We compared GC incidence between PCAB users and histamine type-2 receptor antagonist (H2RA) users, matching them on the basis of propensity scores calculated with considerations for age, sex, smoking, alcohol consumption, comorbidities, and co-administered medications. PCABs included only vonoprazan in this study. RESULTS: Among 54,055 patients, 568 (1.05%) developed GC during the follow-up period (mean, 3.65 years). The cumulative incidence of GC was 1.64% at 3 years, 2.02% at 4 years, and 2.36% at 5 years in PCAB users and 0.71% at 3 years, 1.04% at 4 years, and 1.22% at 5 years in H2RA users. The use of PCABs was associated with a higher GC risk (matched hazard ratio, 1.92; 95% confidence interval, 1.13-3.25; P = .016). Longer PCAB use and high-dose PCAB use were significantly associated with higher incidence of GC. Sensitivity analyses showed the risk of GC incidence among PCAB users was comparable with that of PPI users. CONCLUSIONS: The use of PCABs was associated with an increased risk of GC among Hp-eradicated patients, with duration/dose response effects.
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Infecciones por Helicobacter , Inhibidores de la Bomba de Protones , Pirroles , Neoplasias Gástricas , Sulfonamidas , Humanos , Masculino , Femenino , Neoplasias Gástricas/epidemiología , Infecciones por Helicobacter/complicaciones , Persona de Mediana Edad , Japón/epidemiología , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Anciano , Incidencia , Pirroles/efectos adversos , Pirroles/uso terapéutico , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/administración & dosificación , Helicobacter pylori , Antagonistas de los Receptores H2 de la Histamina/efectos adversos , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Antagonistas de los Receptores H2 de la Histamina/administración & dosificación , Estudios Retrospectivos , Adulto , Medición de Riesgo , Factores de Riesgo , Antibacterianos/efectos adversos , Antibacterianos/uso terapéuticoRESUMEN
INTRODUCTION: Intravenous corticosteroids are the mainstay of treatment of patients hospitalized with acute severe ulcerative colitis (ASUC). However, 30%-40% of the patients are refractory to corticosteroids. We investigated whether addition of tofacitinib to corticosteroids improved the treatment responsiveness in patients with ASUC. METHODS: This single-center, double-blind, placebo-controlled trial randomized adult patients with ASUC (defined by the Truelove Witts severity criteria) to receive either tofacitinib (10 mg thrice daily) or a matching placebo for 7 days while continuing intravenous corticosteroids (hydrocortisone 100 mg every 6 hours). The primary end point was response to treatment (decline in the Lichtiger index by >3 points and an absolute score <10 for 2 consecutive days without the need for rescue therapy) by day 7. The key secondary outcome was the cumulative probability of requiring initiation of infliximab or undergoing colectomy within 90 days following randomization. All analyses were performed in the intention-to-treat population. RESULTS: A total of 104 patients were randomly assigned to a treatment group (53 to tofacitinib and 51 to placebo). At day 7, response to treatment was achieved in 44/53 (83.01%) patients receiving tofacitinib vs 30/51 (58.82%) patients receiving placebo (odds ratio 3.42, 95% confidence interval 1.37-8.48, P = 0.007). The need for rescue therapy by day 7 was lower in the tofacitinib arm (odds ratio 0.27, 95% confidence interval 0.09-0.78, P = 0.01). The cumulative probability of need for rescue therapy at day 90 was 0.13 in patients who received tofacitinib vs 0.38 in patients receiving placebo (log-rank P = 0.003). Most of the treatment-related adverse effects were mild. One patient, receiving tofacitinib, developed dural venous sinus thrombosis. DISCUSSION: In patients with ASUC, combination of tofacitinib and corticosteroids improved treatment responsiveness and decreased the need for rescue therapy.
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Colitis Ulcerosa , Piperidinas , Pirimidinas , Pirroles , Humanos , Piperidinas/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Pirimidinas/uso terapéutico , Masculino , Femenino , Método Doble Ciego , Adulto , Pirroles/uso terapéutico , Pirroles/administración & dosificación , Persona de Mediana Edad , Enfermedad Aguda , Resultado del Tratamiento , Índice de Severidad de la Enfermedad , Quimioterapia Combinada , Inhibidores de Proteínas Quinasas/uso terapéutico , Colectomía , Infliximab/uso terapéuticoRESUMEN
INTRODUCTION: Patients with ulcerative colitis (UC) receiving immunosuppressive drugs are at substantial risk of colectomy. We aimed to assess the risk of postoperative complications of tofacitinib exposure before colectomy in comparison with biologics. METHODS: A multicenter, retrospective, observational study was conducted in patients with UC who underwent total colectomy for medically refractory disease, exposed to tofacitinib or a biologic before surgery. Primary outcome was the occurrence of any complication within 30 (early) and 90 (late) days after surgery. Secondary outcomes were the occurrence of infections, sepsis, surgical site complications, venous thromboembolic events (VTE), hospital readmissions, and redo surgery within the same timepoints. RESULTS: Three hundred one patients (64 tofacitinib, 162 anti-tumor necrosis factor-α agents, 54 vedolizumab, and 21 ustekinumab) were included. No significant differences were reported in any outcome, except for a higher rate of early VTE with anti-tumor necrosis factor-α agents ( P = 0.047) and of late VTE with vedolizumab ( P = 0.03). In the multivariate analysis, drug class was not associated with a higher risk of any early and late complications. Urgent colectomy increased the risk of any early (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.06-3.48) complications, early hospital readmission (OR 4.79, 95% CI 1.12-20.58), and early redo surgery (OR 7.49, 95% CI 1.17-47.85). A high steroid dose increased the risk of any early complications (OR 1.96, 95% CI 1.08-3.57), early surgical site complications (OR 2.03, 95% CI 1.01-4.09), and early redo surgery (OR 7.52, 95% CI 1.42-39.82). Laparoscopic surgery decreased the risk of any early complications (OR 0.54, 95% CI 0.29-1.00), early infections (OR 0.39, 95% CI 0.18-0.85), and late hospital readmissions (OR 0.34, 95% CI 0.12-1.00). DISCUSSION: Preoperative tofacitinib treatment demonstrated a postoperative safety profile comparable with biologics in patients with UC undergoing colectomy.
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Productos Biológicos , Colectomía , Colitis Ulcerosa , Piperidinas , Complicaciones Posoperatorias , Pirimidinas , Humanos , Colitis Ulcerosa/cirugía , Colitis Ulcerosa/tratamiento farmacológico , Masculino , Femenino , Piperidinas/uso terapéutico , Piperidinas/efectos adversos , Pirimidinas/uso terapéutico , Pirimidinas/efectos adversos , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Productos Biológicos/uso terapéutico , Productos Biológicos/efectos adversos , Complicaciones Posoperatorias/epidemiología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Readmisión del Paciente/estadística & datos numéricos , Pirroles/uso terapéutico , Pirroles/efectos adversos , Tromboembolia Venosa/epidemiología , Reoperación/estadística & datos numéricos , Infección de la Herida Quirúrgica/epidemiología , AncianoRESUMEN
OBJECTIVES: Inflammatory cytokines that signal through the Janus kinases-signal transducer and activator of transcription (JAK-STAT) pathway, especially interferons (IFNs), are implicated in Sjögren's disease (SjD). Although inhibition of JAKs is effective in other autoimmune diseases, a systematic investigation of IFN-JAK-STAT signalling and the effect of JAK inhibitor (JAKi) therapy in SjD-affected human tissues has not been fully investigated. METHODS: Human minor salivary glands (MSGs) and peripheral blood mononuclear cells (PBMCs) were investigated using bulk or single-cell (sc) RNA sequencing (RNAseq), immunofluorescence (IF) microscopy and flow cytometry. Ex vivo culture assays on PBMCs and primary salivary gland epithelial cell (pSGEC) lines were performed to model changes in target tissues before and after JAKi. RESULTS: RNAseq and IF showed activated JAK-STAT pathway in SjD MSGs. Elevated IFN-stimulated gene (ISGs) expression associated with clinical variables (eg, focus scores, anti-SSA positivity). scRNAseq of MSGs exhibited cell type-specific upregulation of JAK-STAT and ISGs; PBMCs showed similar trends, including markedly upregulated ISGs in monocytes. Ex vivo studies showed elevated basal pSTAT levels in SjD MSGs and PBMCs that were corrected with JAKi. SjD-derived pSGECs exhibited higher basal ISG expressions and exaggerated responses to IFN-ß, which were normalised by JAKi without cytotoxicity. CONCLUSIONS: SjD patients' tissues exhibit increased expression of ISGs and activation of the JAK-STAT pathway in a cell type-dependent manner. JAKi normalises this aberrant signalling at the tissue level and in PBMCs, suggesting a putative viable therapy for SjD, targeting both glandular and extraglandular symptoms. Predicated on these data, a phase Ib/IIa randomised controlled trial to treat SjD with tofacitinib was initiated.
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Inhibidores de las Cinasas Janus , Quinasas Janus , Leucocitos Mononucleares , Factores de Transcripción STAT , Glándulas Salivales Menores , Transducción de Señal , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/tratamiento farmacológico , Síndrome de Sjögren/inmunología , Inhibidores de las Cinasas Janus/farmacología , Inhibidores de las Cinasas Janus/uso terapéutico , Transducción de Señal/efectos de los fármacos , Quinasas Janus/metabolismo , Factores de Transcripción STAT/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Glándulas Salivales Menores/inmunología , Femenino , Interferones , Piperidinas/farmacología , Piperidinas/uso terapéutico , Persona de Mediana Edad , Masculino , Pirimidinas/farmacología , Pirimidinas/uso terapéutico , Adulto , Inflamación , Pirroles/farmacología , Pirroles/uso terapéutico , Células Epiteliales/efectos de los fármacosRESUMEN
OBJECTIVE: Information on the persistence of tofacitinib (TOF) in psoriatic arthritis (PsA) is scarce in real-world conditions. Our objective was to analyze the persistence and safety of TOF under these conditions. METHODS: This was a single-center retrospective longitudinal observational study of all patients with PsA who received at least 1 dose of TOF. The main focus was on adverse events (AEs) and drug survival. Drug survival was analyzed by Kaplan-Meier curves and persistence explanatory factors by multivariate Cox regression models. The hazard ratio (HR) was used to measure association. RESULTS: Seventy-two patients were included, 54 women and 18 men, mean age 51.9 (SD 11.1) years, mean disease duration of 10.4 (SD 6.99) years. TOF was ≥ third line of therapy in > 70% of cases. The median survival was 13.0 (IQR 5.3-29.0) months. One-year retention rate was 52.7% (95% CI 42.4-65.6). TOF survival was not influenced by sex, disease duration, comorbidities, or line of treatment. Younger patients (HR 0.96, P = 0.01) and those with enthesitis (HR 0.37, P = 0.03) showed lower odds of drug discontinuation. The overall rate of AEs was 52.9 (95% CI 38.5-70.6)/100 person-years. Most AEs occurred during the first 6 months of exposure. CONCLUSION: In this real-world study, TOF showed a reasonably good retention rate in a PsA population that was mostly refractory to biologic and oral targeted synthetic disease-modifying antirheumatic drugs. There were no new causes for concern regarding safety. Patients with refractory PsA and enthesitis might be a specific target population for this drug.
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Artritis Psoriásica , Piperidinas , Pirimidinas , Humanos , Artritis Psoriásica/tratamiento farmacológico , Masculino , Femenino , Piperidinas/uso terapéutico , Piperidinas/efectos adversos , Persona de Mediana Edad , Estudios Retrospectivos , Pirimidinas/uso terapéutico , Pirimidinas/efectos adversos , Adulto , Estudios Longitudinales , Resultado del Tratamiento , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Entesopatía/tratamiento farmacológico , Entesopatía/inducido químicamente , Pirroles/uso terapéutico , Pirroles/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversosRESUMEN
OBJECTIVE: This post hoc analysis assessed the effect of baseline C-reactive protein (CRP) on the efficacy and safety of tofacitinib (TOF) use in ankylosing spondylitis (AS), as well as patient-reported outcomes (PROs). METHODS: Phase II (ClinicalTrials.gov: NCT01786668) and phase III (ClinicalTrials.gov: NCT03502616) data from patients with active AS were used. Endpoints (weeks 12, 16, and 48), including 20% and 40% improvement in Assessment of SpondyloArthritis international Society (ASAS), AS Disease Activity Score with CRP low disease activity, 50% improvement in Bath AS Disease Activity Index (BASDAI50), and PROs (pain and fatigue), were stratified by baseline CRP (mg/L) as follows: < 5 (normal), ≥ 5 (elevated), < 10, and ≥ 10. Safety outcomes were evaluated between < 5 and ≥ 5 mg/L subgroups. RESULTS: Overall, 372 patients were included (69.6% ≥ 5mg/L; 50.8% ≥ 10 mg/L). At baseline in the < 5mg/L group, more placebo-treated than TOF-treated patients received concomitant nonsteroidal antiinflammatory drugs (NSAIDs) or sulfasalazine (SSZ). Week 12 efficacy and PRO responses were generally higher for TOF vs placebo, regardless of baseline CRP. The treatment effect (placebo-adjusted response) at week 12 was generally numerically higher in ≥ 5 mg/L and ≥ 10 mg/L vs < 5 mg/L and < 10 mg/L groups. Incidence rates for treatment-emergent adverse events (TEAEs) and "all infections" were numerically higher for TOF vs placebo in patients in the < 5 mg/L group, but similar for TOF vs placebo in patients in the ≥ 5 mg/L group. CONCLUSION: Regardless of baseline CRP, TOF was more efficacious vs placebo at week 12. The placebo-adjusted efficacy and PRO responses were generally numerically higher in patients with CRP ≥ 5 mg/L and ≥ 10 mg/L vs < 5 mg/L and < 10 mg/L. The higher concomitant NSAID/SSZ exposure may have improved efficacy responses in the baseline < 5 mg/L placebo group, and ultimately affected the TOF treatment effect. Safety was consistent with previous studies of TOF use in AS, with numerically higher incidence rates for TEAEs and "all infections" for TOF vs placebo in patients with CRP < 5 mg/L.
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Proteína C-Reactiva , Piperidinas , Pirimidinas , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante , Humanos , Espondilitis Anquilosante/tratamiento farmacológico , Pirimidinas/uso terapéutico , Pirimidinas/efectos adversos , Piperidinas/uso terapéutico , Piperidinas/efectos adversos , Proteína C-Reactiva/análisis , Masculino , Femenino , Adulto , Resultado del Tratamiento , Persona de Mediana Edad , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Medición de Resultados Informados por el Paciente , Pirroles/uso terapéutico , Pirroles/efectos adversos , Método Doble CiegoRESUMEN
BACKGROUND: This study aims to evaluate the efficacy and safety of vonoprazan-amoxicillin (VA), vonoprazan-amoxicillin-clarithromycin (VAC), vonoprazan-based bismuth-containing quadruple therapy (VBQT), and PPI-based triple (PAC) or quadruple therapy (PBQT) for H. pylori infection with the consideration of duration of therapy and amoxicillin dose (H: high; L: low). MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials (RCTs) up to December 15, 2023. The efficacy outcome was eradication rate, and safety outcomes included the rates of adverse events and treatment discontinuation. RESULTS: Twenty-seven RCTs were included. The pooled eradication rates were 82.8% for VA, 89.1% for VAC, and 91.8% for VBQT, which increased with the higher amoxicillin frequency of administration and extended duration of therapy within each regimen. There were no significant differences in eradication rate when comparing 7-VA versus 7-VAC and 14-VA versus 14-VAC. VA was at least comparable to PAC. The eradication rate did not differ significantly between 10-H-VA or 14-H-VA versus 14-PBQT. 7-L-VAC demonstrated higher eradication rate versus 7-PAC and comparable rate to 14-PAC. 14-VBQT showed higher eradication rates versus 14-PBQT. The adverse events rate was 19.3% for VA, 30.6% for VAC, and 38.4% for VBQT. VA had similar risk of adverse events versus VAC and significantly fewer adverse events compared to PBQT. The treatment discontinuation rate did not differ significantly between treatments. CONCLUSIONS: The eradication rate of VBQT was the highest at above 90% followed by VAC and VA. VA was as effective as VAC and superior to PPI-based therapies with favorable safety, highlighting the potential of VA therapy as a promising alternative to traditional PPI-based therapies. VPZ-based triple or quadruple therapies was more effective than PPI-based therapies. Further studies are needed to establish the optimal treatment regimen especially in the western countries.
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Amoxicilina , Antibacterianos , Infecciones por Helicobacter , Helicobacter pylori , Inhibidores de la Bomba de Protones , Pirroles , Sulfonamidas , Humanos , Amoxicilina/uso terapéutico , Amoxicilina/administración & dosificación , Amoxicilina/efectos adversos , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Antibacterianos/administración & dosificación , Claritromicina/uso terapéutico , Claritromicina/efectos adversos , Quimioterapia Combinada , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/administración & dosificación , Pirroles/uso terapéutico , Pirroles/administración & dosificación , Pirroles/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Sulfonamidas/uso terapéutico , Sulfonamidas/efectos adversos , Sulfonamidas/administración & dosificación , Resultado del TratamientoRESUMEN
BACKGROUND: The amoxicillin dose used in dual therapy to eradicate Helicobacter pylori varies across studies and the optimal amoxicillin dose for vonoprazan-based dual therapies remains unclear. We aimed to investigate the efficacy and safety of low- and high-dose amoxicillin in vonoprazan-amoxicillin dual therapy. MATERIALS AND METHODS: A comprehensive systematic review was conducted by searching databases from inception to October 2023. All trials that evaluated the effectiveness and safety of vonoprazan-amoxicillin dual therapy for eradicating H. pylori were included. Pooled eradication rate, incidence of adverse events, relative risks, and 95% confidence intervals are presented. RESULTS: Eighteen studies with 12 low-dose amoxicillin (VLA) and 13 high-dose amoxicillin (VHA) arms were included. The pooled eradication rates were 82.4% and 86.8% for VLA therapy, and 86.0% and 90.9% for VHA therapy by the intention-to-treat and per-protocol analyses, respectively. In the subgroup analysis stratified by duration, the eradication rates achieved in 7 days, 10 days, and 14 days treatments with VLA and VHA dual therapies were 80.8%, 84.2%, 83.1%, and 67.3%, 88.8%, 87.5%, respectively. In the four randomized controlled trials that directly compared VLA and VHA dual therapies, the efficacy was not statistically different in the intention-to-treat (76.9% vs 81.4%, p = 0.337) and per-protocol (81.6% vs 84.0%, p = 0.166) analyses. Additionally, the incidence of adverse events (p = 0.965) and compliance (p = 0.994) were similar in both groups. CONCLUSION: VLA therapy demonstrated comparable efficacy and safety to VHA therapy, along with regional differences. An appropriately extended treatment duration may be critical for therapeutic optimization of vonoprazan-amoxicillin treatment.
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Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Pirroles , Sulfonamidas , Amoxicilina/administración & dosificación , Amoxicilina/uso terapéutico , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/efectos adversos , Pirroles/administración & dosificación , Pirroles/uso terapéutico , Pirroles/efectos adversos , Helicobacter pylori/efectos de los fármacos , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Resultado del Tratamiento , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/efectos adversosRESUMEN
BACKGROUND: The effect of preprandial or postprandial administration of amoxicillin on the efficacy of vonoprazan-amoxicillin dual therapy (VA-dual therapy) for Helicobacter pylori treatment has not been studied. It is also unclear whether amoxicillin dosing four times daily is more effective than three times daily. We aimed to investigate the effect of different amoxicillin administration regimens on the efficacy of VA-dual therapy. MATERIALS AND METHODS: H. pylori-infected subjects were randomly assigned to three groups in a 1:1:1 ratio to receive a 14-day dual therapy consisting of vonoprazan 20 mg twice daily + amoxicillin 1000 mg three times daily before meals (BM-TID) or 1000 mg three times daily after meals (AM-TID) or 750 mg four times daily after meals (AM-QID). H. pylori eradication rates, adverse events rates, compliance, and antibiotic resistance were compared. RESULTS: Between May 2021 to April 2023, 327 subjects were enrolled. The eradication rates of BM-TID, AM-TID, and AM-QID dual therapy were 88.1%, 89.9%, and 93.6% in intention-to-treat (ITT) analysis, 90.6%, 94.2%, and 99.0% in modified ITT (MITT) analysis, and 90.4%, 94.1%, and 99.0% in per-protocol (PP) analysis. Although there was non-inferiority between BM-TID and AM-TID, as well as between AM-TID and AM-QID, AM-QID was significantly more effective than BM-TID. There were no significant differences in adverse event rates, compliance, and antibiotic resistance among the three groups. CONCLUSIONS: Postprandial administration and the increased frequency of administration of amoxicillin may contribute to a better efficacy of VA-dual therapy, especially for rescue therapy. All VA-dual therapy in our study could achieve good efficacy for first-line treatment. TRIAL REGISTRATION: clinicaltrials.gov: NCT05901051.
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Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Pirroles , Sulfonamidas , Humanos , Amoxicilina/administración & dosificación , Amoxicilina/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Masculino , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/efectos adversos , Femenino , Persona de Mediana Edad , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Helicobacter pylori/efectos de los fármacos , Pirroles/administración & dosificación , Pirroles/uso terapéutico , Resultado del Tratamiento , Anciano , Adulto , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéutico , Esquema de MedicaciónRESUMEN
BACKGROUND: Gastroesophageal reflux disease (GERD) symptoms frequently recur after cessation of acid blockers. The presence of a hiatal hernia may worsen GERD symptoms and increase the risk of esophageal malignancy. The aim of this study is to clarify the timing and predictors for recurrence of GERD symptoms after cessation of vonoprazan (VPZ) therapy. METHODS: A retrospective observational study involved 86 patients who underwent cessation of VPZ therapy for symptomatic GERD. Collated data from medical record review included the endoscopic findings and Izumo scale score. RESULTS: The mean duration of continuous VPZ therapy before cessation was 7.9 months. GERD symptoms requiring the resumption of VPZ therapy recurred in 66 of 86 patients (77%). Kaplan-Meier analysis showed that overall recurrence-free rates at 6 months, one and two years after VPZ cessation were 44%, 32% and 23%, respectively. Alcohol use, the presence of a hiatal hernia and long-term therapy for more than six months were identified as significant positive predictors for symptomatic recurrence. Notably, hiatal hernia had the highest hazard ratio in both univariate and multivariate analyses. The recurrence-free rate in patients with a hiatal hernia was much lower at 6 months than in patients without a hiatal hernia (15% and 51%, respectively p = 0.002). After the symptomatic recurrence, GERD symptoms improved significantly after one-month VPZ therapy. CONCLUSION: The rate of symptomatic recurrence after VPZ cessation in patients with GERD is considerable. Cessation of acid suppression therapy should be cautious in patients with both a hiatal hernia and GERD.
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Reflujo Gastroesofágico , Hernia Hiatal , Inhibidores de la Bomba de Protones , Pirroles , Recurrencia , Sulfonamidas , Humanos , Masculino , Femenino , Hernia Hiatal/complicaciones , Estudios Retrospectivos , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Reflujo Gastroesofágico/tratamiento farmacológico , Reflujo Gastroesofágico/complicaciones , Persona de Mediana Edad , Anciano , Pirroles/uso terapéutico , Pirroles/efectos adversos , Pirroles/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Estimación de Kaplan-Meier , Factores de Riesgo , Modelos de Riesgos Proporcionales , Adulto , Análisis MultivarianteRESUMEN
BACKGROUND: In Chinese healthcare settings, drug selection decisions are predominantly influenced by the Pharmacy & Therapeutics Committee (PTC). This study evaluates two recently introduced potassium-competitive acid blockers, vonoprazan (VPZ) and tegoprazan (TPZ), utilizing the Evidence and Value: Impact on DEcisionMaking (EVIDEM) framework. METHODS: The study employed the 10th edition of EVIDEM, which includes a core model with five domains and 13 criteria. Two independent expert panels were involved: the PTC expert panel, tasked with assigning weights using a 5-point scale, defining scoring indicators, examining the evidence matrix, scoring, and decision-making; and the evidence matrix expert panel, responsible for conducting a systematic literature review, creating the evidence matrix, and evaluating the value contributions of VPZ and TPZ. RESULTS: The analysis estimated the value contributions of VPZ and TPZ to be 0.59 and 0.54, respectively. The domain of 'economic consequences of intervention' showed the most significant variation in value contribution between the two drugs, followed by 'comparative outcomes of intervention' and 'type of benefit of intervention'. CONCLUSION: Employing the EVIDEM framework, VPZ's value contribution was found to be marginally superior to that of TPZ. The EVIDEM framework demonstrates potential for broader application in Chinese medical institutions.
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Reflujo Gastroesofágico , Inhibidores de la Bomba de Protones , Pirroles , Sulfonamidas , Sulfonamidas/uso terapéutico , Pirroles/uso terapéutico , Humanos , Inhibidores de la Bomba de Protones/uso terapéutico , China , Reflujo Gastroesofágico/tratamiento farmacológico , Técnicas de Apoyo para la Decisión , Análisis Costo-BeneficioRESUMEN
BACKGROUND: Both vonoprazan and proton pump inhibitors (PPIs) are currently used to treat artificial ulcers after gastric endoscopic submucosal dissection. However, evidence-based medicine proving the efficacy of vonoprazan is still lacking. Therefore, this meta-analysis aimed to compare the efficacy of vonoprazan and PPIs for the treatment of artificial ulcers after gastric endoscopic submucosal dissection. METHODS: The PubMed, EMBASE and Cochrane Library databases were searched up to September 2023 for related randomized controlled trials (RCTs). RCTs that compared the efficacy of vonoprazan and PPIs in treating artificial gastric ulcers after gastric endoscopic submucosal dissection were included. Two independent reviewers screened the included studies, extracted the data and assessed the risk of bias. The following outcomes were extracted for comparison: ulcer healing rate, ulcer shrinkage rate, delayed postoperative bleeding rate, and ulcer perforation rate. RESULTS: Nine randomized controlled trials involving 926 patients were included. The pooled results showed that vonoprazan had a significantly lower rate of delayed postoperative bleeding than did PPIs (RR = 0.46; 95% CI = 0.23-0.91; P = 0.03). No significant differences were found in terms of ulcer healing, shrinkage rates, or ulcer perforation rates between vonoprazan and PPIs. CONCLUSIONS: Compared with PPIs, vonoprazan is superior at reducing delayed postoperative bleeding after endoscopic submucosal dissection. However, further studies are needed to prove the efficacy of vonoprazan. SYSTEMATIC REVIEW REGISTRATION: Identifier CRD42024509227.
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Resección Endoscópica de la Mucosa , Inhibidores de la Bomba de Protones , Pirroles , Ensayos Clínicos Controlados Aleatorios como Asunto , Úlcera Gástrica , Sulfonamidas , Humanos , Inhibidores de la Bomba de Protones/uso terapéutico , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Sulfonamidas/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/etiología , Pirroles/uso terapéutico , Hemorragia Posoperatoria/etiología , Hemorragia Posoperatoria/prevención & control , Resultado del TratamientoRESUMEN
BACKGROUND: Systemic immunomodulatory agents are indicated in the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis. Perioperative use of these medications may increase the risk of surgical site infection (SSI) and complication. OBJECTIVE: To evaluate the risk of SSI and complication in patients with chronic autoimmune inflammatory disease receiving immunomodulatory agents (tumor necrosis factor-alfa [TNF-α] inhibitors, interleukin [IL] 12/23 inhibitor, IL-17 inhibitors, IL-23 inhibitors, cytotoxic T-lymphocyte-associated antigen-4 costimulator, phosphodiesterase-4 inhibitor, Janus kinase inhibitors, tyrosine kinase 2 inhibitor, cyclosporine (CsA), and methotrexate [MTX]) undergoing surgery. METHODS: We performed a search of the MEDLINE PubMed database of patients with chronic autoimmune inflammatory disease on immune therapy undergoing surgery. RESULTS: We examined 48 new or previously unreviewed studies; the majority were retrospective studies in patients with rheumatoid arthritis and inflammatory bowel disease. CONCLUSION: For low-risk procedures, TNF-α inhibitors, IL-17 inhibitors, IL-23 inhibitors, ustekinumab, abatacept, MTX, CsA, and apremilast can safely be continued. For intermediate- and high-risk surgery, MTX, CsA, apremilast, abatacept, IL-17 inhibitors, IL-23 inhibitors, and ustekinumab are likely safe to continue; however, a case-by-case approach is advised. Acitretin can be continued for any surgery. There is insufficient evidence to make firm recommendations on tofacitinib, upadacitinib, and deucravacitinib.