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BACKGROUND & AIMS: We conducted a network meta-analysis to compare the efficacy of advanced therapies for achieving endoscopic outcomes in patients with moderate-to-severely active Crohn's disease. METHODS: MEDLINE, Embase, and Cochrane CENTRAL databases were searched from inception to August 2, 2023 to identify phase II and III randomized controlled trials (RCTs) in adults (≥18 years) with moderate-to-severe Crohn's disease treated with tumor necrosis factor (TNF) antagonists, etrolizumab, vedolizumab, anti-interleukin (IL)12/23p40, anti-IL23p19, or Janus kinase-1 (JAK1) inhibitors, compared with placebo/active comparator, for induction and/or maintenance of remission and reported endoscopic outcomes. Primary outcome was endoscopic response after induction therapy, and endoscopic remission after maintenance therapy. We performed a random-effects network meta-analysis using a frequentist approach, and estimated relative risk (RRs), 95% confidence interval (CI) values, and P score for ranking agents. We used GRADE to ascertain certainty of evidence. RESULTS: A total of 20 RCTs (19 placebo-controlled and 1 head-to-head trial; 5592 patients) were included out of which 12 RCTs reported endoscopic outcomes for the induction phase, 5 reported for the maintenance phase, and 3 reported for both induction and maintenance phases. JAK1 inhibitors (RR, 3·49 [95% CI, 1·48-8·26]) and anti-IL23p19 (RR, 2·30 [95% CI, 1·02-5·18]) agents were more efficacious than etrolizumab (moderate certainty of evidence), and JAK1 inhibitors (RR, 2·34 [95% CI, 1·14-4·80]) were more efficacious than anti-IL12/23p40 agents for inducing endoscopic response (moderate certainty of evidence). JAK1 inhibitors and anti-IL23p19 ranked highest for induction of endoscopic response. There was paucity of RCTs of TNF antagonists reporting endoscopic outcomes with induction therapy. On network meta-analysis of 6 RCTs, all agents except vedolizumab (RR, 1.89 [95% CI, 0.61-5.92]) were effective in maintaining endoscopic remission compared with placebo. TNF antagonists, IL12/23p40, and JAK1 inhibitors were ranked highest. CONCLUSIONS: On network meta-analysis, JAK1 inhibitors and anti-IL23p19 agents may be the most effective among non-TNF-targeting advanced therapies for inducing endoscopic response. Future head-to-head trials will further inform positioning of different therapies for the management of Crohn's disease.
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Enfermedad de Crohn , Metaanálisis en Red , Humanos , Enfermedad de Crohn/tratamiento farmacológico , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Fármacos Gastrointestinales/uso terapéuticoRESUMEN
BACKGROUND & AIMS: Proactive therapeutic drug monitoring (TDM) has been proposed to improve outcomes in patients with inflammatory bowel disease (IBD) treated with tumor necrosis factor (TNF)α antagonists. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing proactive TDM with conventional management in patients with IBD. METHODS: We identified RCTs in patients with IBD treated with TNFα antagonists comparing proactive TDM (routine assessments of trough concentration with dose adjustments to maintain predetermined trough concentration, regardless of disease activity) with conventional management (clinically driven dose adjustments). The primary outcome was failure to maintain clinical remission. Certainty of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluations. RESULTS: On meta-analysis of 9 RCTs (8 RCTs in adults, and focusing on maintenance phase), there was no significant difference in the risk of failing to maintain clinical remission in patients who underwent proactive TDM (267/709; 38%) vs conventional management (292/696; 42%) (relative risk [RR], 0.96; 95% confidence interval [CI], 0.81-1.13) with moderate heterogeneity (inconsistency index = 36%) (Grading of Recommendations, Assessment, Development and Evaluations; low certainty evidence), with no differences in patients with Crohn's disease (RR, 0.87 ; 95% CI, 0.66-1.15) and ulcerative colitis (RR, 0.88; 95% CI, 0.72-1.07). Disease duration, concomitant immunomodulators, disease activity at baseline, and optimization of therapy before randomization did not modify this association. No differences were observed in risk of developing antidrug antibodies or serious adverse events. Patients in the proactive TDM arm were more likely to undergo dose escalation (RR, 1.56; 95% CI, 1.25-1.94). CONCLUSIONS: Routine proactive TDM to target biologic concentration to specific thresholds, regardless of disease activity, did not offer clinical benefit in patients with IBD treated with TNFα antagonists in RCTs conducted to date. We cannot exclude the possibility of benefit in disease subtypes and phases of therapy (induction) not represented in these RCT populations.
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Productos Biológicos , Enfermedades Inflamatorias del Intestino , Adulto , Productos Biológicos/uso terapéutico , Monitoreo de Drogas , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Inducción de Remisión , Factor de Necrosis Tumoral alfaRESUMEN
INTRODUCTION: To assess the safety of early vs late biologic switch in patients with inflammatory bowel disease. METHODS: In this retrospective study, we included patients with inflammatory bowel disease who underwent biologic switch between January 2014 and July 2022 at a tertiary center. The primary outcome was any infection by 6 months. RESULTS: There was no statistically significant difference between patients who had early biologic switch (≤30 days, n = 51) and late switch (>30 days, n = 77) in either infectious or noninfectious adverse events by 6 and 12 months. DISCUSSION: Early biologic switch is safe. A prolonged washout period between 2 biologics is unnecessary.
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Productos Biológicos , Enfermedades Inflamatorias del Intestino , Humanos , Estudios Retrospectivos , Canadá , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/inducido químicamente , Productos Biológicos/efectos adversosRESUMEN
INTRODUCTION: We performed a systematic review to investigate whether patients with Crohn's disease (CD) and permanent ileostomy (PI) have been included in clinical trials evaluating biologics and small molecules. METHODS: MEDLINE, Embase and Cochrane library (CENTRAL) data bases were searched from inception to May 16, 2022 for placebo controlled induction and/or maintenance randomized controlled trials assessing biologics and oral small molecules in adult patients with active CD. RESULTS: Of the 81 induction and maintenance trials assessing biologics and oral small molecules in CD, none permitted the enrollment of patients with PI. Patients with CD and PI have been universally excluded from pharmaceutical trials of biologics and small molecules to date. DISCUSSION: There is an urgent need to identify barriers to enrollment and develop eligibility and outcome measures enabling the inclusion of patients with CD and PI into clinical trials.
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Productos Biológicos , Enfermedad de Crohn , Adulto , Humanos , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/cirugía , Ileostomía , Productos Biológicos/uso terapéutico , Inducción de RemisiónRESUMEN
INTRODUCTION: Chronic isolated terminal ileitis (TI) may be seen in Crohn's disease (CD) and intestinal tuberculosis (ITB) in addition to other etiologies that may be managed symptomatically. We developed a revised algorithm to distinguish patients with a specific etiology from a nonspecific etiology. METHODS: Patients with chronic isolated TI followed up from 2007 to 2022 were retrospectively reviewed. A specific (ITB or CD) diagnosis was made based on standardized criteria, and other relevant data were collected. Using this cohort, validation of a previously suggested algorithm was conducted. Furthermore, based on the results of a univariate analysis, a multivariate analysis with bootstrap validation was used to develop a revised algorithm. RESULTS: We included 153 patients (mean age 36.9 ± 14.6 years, males-70%, median duration-1.5 years, range: 0-20 years) with chronic isolated TI of whom 109 (71.2%) received a specific diagnosis (CD-69, ITB-40). On multivariate regression and validation statistics with a combination of clinical, laboratory, radiological, and colonoscopic findings, an optimism corrected c-statistic of 0.975 and 0.958 was obtained with and without histopathological findings, respectively. Revised algorithm, based on these, showed sensitivity, specificity, positive and negative predictive values, and overall accuracy of 98.2% (95% CI: 93.5-99.8), 75.0% (95% CI: 59.7-86.8), 90.7% (95% CI: 85.4-94.2), 94.3% (95% CI: 80.5-98.5) and 91.5%(95% CI:85.9-95.4), respectively. This was more sensitive and specific than the previous algorithm (accuracy 83.9%, sensitivity 95.5%, and specificity 54.6%). DISCUSSION: We developed a revised algorithm and a multimodality approach to stratify patients with chronic isolated TI into specific and nonspecific etiologies with an excellent diagnostic accuracy, which could potentially avoid missed diagnosis and unnecessary side effects of treatment.
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Enfermedad de Crohn , Tuberculosis Gastrointestinal , Masculino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Enfermedad de Crohn/patología , Estudios Retrospectivos , Colonoscopía , Valor Predictivo de las Pruebas , Radiografía , Diagnóstico Diferencial , Tuberculosis Gastrointestinal/diagnósticoRESUMEN
PURPOSE OF REVIEW: Inflammatory bowel disease (IBD) is complex disease that poses significant economic, and psychological burden on patients. Despite advent of newer biologics and small molecules targeting different aspects of immunopathogenesis, there appears to be a plateau in clinical outcomes. In this review we discuss the role of multiple biologics, existing evidence and various considerations when prescribing multiple biologics. RECENT FINDINGS: Recent scientific advances helped to unravel the pathophysiology of inflammatory bowel disease and newer cytokines have been identified which can be potential targets in the management of IBD. Targeting more than one cytokine appears to be logical solution to break the therapeutic ceiling to improve clinical outcomes in IBD. The combination biologics appear safe and effective; however, the available evidence is limited. Refractory IBD, presence of other immune mediated inflammatory diseases and extra intestinal manifestations are currently the common considerations of combination biologics in IBD. SUMMARY: Inflammatory bowel disease is a complex immune mediated disease with diverse clinical presentation and often has a complicated clinical course requiring multidisciplinary management. As the number of targeted therapies increases so does the concern on their safety and efficacy. Combination biologics though may appear to be safe, we need well designed prospective studies for firm conclusions.
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Productos Biológicos , Enfermedades Inflamatorias del Intestino , Productos Biológicos/uso terapéutico , Citocinas , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Estudios ProspectivosRESUMEN
BACKGROUND AND AIM: Hemostasis in cirrhosis is dynamic and balanced. Thromboelastography (TEG) assesses global coagulation status. We aimed to assess whether TEG-guided blood product transfusions result in lower blood product requirements in patients with cirrhosis undergoing invasive liver-related procedures as compared to the conventional standard of care (SOC). METHODS: In this open-label, randomized controlled trial, cirrhosis patients with coagulopathy, undergoing invasive liver-related procedures, were randomized to either TEG-guided blood product transfusion or SOC. The primary outcome was difference in the amount of fresh frozen plasma (FFP) and platelet units transfused between the two groups. The secondary outcome was procedure-related bleeding complications within 5 days and any complications until 28 days. RESULTS: From November 2017 till June 2019, 58 patients were recruited (29: TEG and 29: SOC). Most common procedures performed were percutaneous liver biopsy (n = 48), followed by transjugular intrahepatic portosystemic shunt (n = 2), percutaneous acetic acid injection (n = 2), and transarterial chemoembolization (n = 2). There were no differences in baseline demographics, hemostatic profile, and types of procedures between the two groups. Only nine patients in TEG group received transfusions compared to all patients in SOC (31% vs 100%; P < 0.001). In TEG group, six (20.7%) received FFP (P = 0.753 vs. SOC), two (6.9%) received platelets (P < 0.001 vs. SOC), and 1(3.4%) patient received both FFP and platelet (P ≥ 0.999 vs. SOC) transfusion. None of the patients in either group developed procedure-related bleeding complications until 5 days post-procedure. The complication rates at 28-day follow-up were similar between the groups. CONCLUSION: TEG-guided blood product transfusion strategy reduces blood product transfusion without increased risk of bleeding in cirrhotic patients undergoing invasive liver-related procedures (CTRI/2017/12/010822).
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Trastornos de la Coagulación Sanguínea/diagnóstico , Transfusión de Componentes Sanguíneos/estadística & datos numéricos , Cirrosis Hepática/sangre , Hemorragia Posoperatoria/prevención & control , Tromboelastografía , Trombocitopenia/sangre , Ácido Acético , Adulto , Biopsia , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/terapia , Quimioembolización Terapéutica , Femenino , Humanos , Biopsia Guiada por Imagen , Inyecciones , Relación Normalizada Internacional , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Selección de Paciente , Plasma , Transfusión de Plaquetas/estadística & datos numéricos , Derivación Portosistémica Intrahepática Transyugular , Hemorragia Posoperatoria/epidemiología , Punciones , Esfinterotomía Endoscópica , Trombocitopenia/etiología , Adulto JovenRESUMEN
Background: Disease extent in Ulcerative Colitis (UC) has prognostic implications for disease course. It is unclear whether the efficacy of medical therapies for moderate to severely active UC vary according to disease extent at enrollment. Methods: We analyzed patient level data from 11 Phase 2 and 3 clinical trials of advanced therapies in patients with moderate-to-severe UC to assess modifications of advanced therapy effects by disease extent. Primary outcome was clinical response and secondary outcomes were clinical remission, endoscopic response/remission and endoscopic improvement, and Mayo clinic subscore for both induction and maintenance studies. Binary and continuous outcomes were analyzed using the modified Poisson regression model and the mixed-effects model, respectively, adjusting for age, sex, disease duration, concomitant steroid use and prior anti-TNF use. Effect modifications with binary outcomes were quantified by ratios of risk ratio for left-sided to that for extensive colitis while effect modifications with the Mayo subscores were quantified by differences of the differences between mean scores of the left-sided and extensive colitis. Results were presented with point estimates and 95% confidence intervals as well as p-values. Findings: Eleven clinical trials enrolling 5450 UC patients (infliximab = 2, adalimumab = 2, golimumab = 2, vedolizumab = 2, tofacitinib = 3) were included. In induction trials, there was evidence to suggest effect modification by disease extent for clinical response with tofacitinib (the ratio of RRs 0.67, 95% CI [0.45, 0.99], p = 0.049) and clinical remission with infliximab (ratio of RRs 0.33, 95% CI [0.13, 0.85], p = 0.020) favoring patients with extensive colitis. There was no evidence to suggest effect modification for endoscopic improvement and clinical outcomes. There was evidence to suggest effect modification by disease extent for clinical remission with tofacitinib (ratio of RRs 0.44, 95% CI [0.22, 0.89], p = 0.020) favoring patients with extensive colitis. For symptom subscores from the Mayo Clinic score, tofacitinib was associated with a greater reduction in both stool frequency (difference of differences 0.37, 95% CI [0.08, 0.65], p = 0.012) and rectal bleeding scores (difference of differences 0.25, 95% CI [0.03, 0.47], p = 0.026) in patients with extensive colitis compared to left sided. Interpretation: These findings underscore the possibility of differential efficacy of medical therapies according to disease distribution. These results warrant further exploration in forthcoming trials to better inform treatment strategies and consideration of disease distribution as a baseline stratification factor in clinical trials. Funding: This study did not receive any financial support.
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BACKGROUND AND AIMS: In this systematic review we summarise existing scoring indices for assessing disease activity and quality of life in perianal fistulising Crohn's disease [PFCD], and highlight gaps in the literature. METHODS: MEDLINE, EMBASE, and CENTRAL were searched from August 24, 2022, to identify studies evaluating clinical, radiological, or patient-reported outcome measures [PROMS] in PFCD. The primary objective was to identify all available scoring indices and describe the operating properties of these indices. RESULTS: A total of 53 studies reported on the use of one clinical index [Perianal Disease Activity Index: PDAI], three PROMs, and 10 radiological indices; 25 studies evaluated the operating properties of these indices. The PDAI demonstrated content validity, construct validity, and responsiveness but criterion validity or reliability were not assessed. The Van Assche Index [VAI], modified VAI, and the Magnetic Resonance Index for Assessing Fistulas in Patients with CD [MAGNIFI-CD] were the most studied radiological indices. These indices demonstrated responsiveness and reliability. The VAI and MAGNIFI-CD demonstrated construct validity; criterion and content validity and feasibility have not been assessed. Among the three PROMs, the Crohn's Anal Fistula Quality of Life index demonstrated content and construct validity, inter-observer reliability, and responsiveness; criterion validity, intra-observer reliability, and feasibility have not been assessed for this index. CONCLUSIONS: There are no fully valid, reliable, and responsive clinical disease or radiological indices for PFCD. Although the radiological indices demonstrated responsiveness and reliability, well-defined cut-offs for response and remission are lacking. Future research should focus on establishing standardised definitions and thresholds for outcomes.
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Enfermedad de Crohn , Calidad de Vida , Fístula Rectal , Índice de Severidad de la Enfermedad , Enfermedad de Crohn/complicaciones , Humanos , Fístula Rectal/etiología , Fístula Rectal/diagnóstico por imagen , Reproducibilidad de los Resultados , Medición de Resultados Informados por el PacienteRESUMEN
BACKGROUND: Exclusive enteral nutrition (EEN) supplementation of the standard of care (SOC) augments steroid responsiveness in patients with acute severe ulcerative colitis (ASUC). EEN is known to alter gut microbial composition. The present study investigates EEN-driven gut microbial alterations in patients with ASUC and examines their correlations with clinical parameters. METHODS: Stool samples from patients with ASUC (nâ =â 44) who received either EEN-supplemented SOC (EEN group; nâ =â 20) or SOC alone (SOC group; nâ =â 24) for 7 days were collected at baseline (day 0) and postintervention (day 7). Microbiome analysis was carried out using 16S ribosomal RNA gene sequencing followed by data processing using QIIME2 and R packages. RESULTS: Seven-day EEN-conjugated corticosteroid therapy in patients with ASUC enhanced the abundances of beneficial bacterial genera Faecalibacterium and Veillonella and reduced the abundance of Sphingomonas (generalized linear model fitted with Lasso regularization with robustness of 100%), while no such improvements in gut microbiota were observed in the SOC group. The EEN-associated taxa correlated with the patient's clinical parameters (serum albumin and C-reactive protein levels). Unlike the SOC group, which retained its preintervention core microbiota, EEN contributed Faecalibacterium prausnitzii, a beneficial gut bacterial taxon, to the gut microbial core. EEN responders showed enhancement of Ligilactobacillus and Veillonella and reduction in Prevotella and Granulicatella. Analysis of baseline gut microbiota showed relative enhancement of certain microbial genera being associated with corticosteroid response and baseline clinical parameters and that this signature could conceivably be used as a predictive tool. CONCLUSIONS: Augmentation of clinical response by EEN-conjugated corticosteroid therapy is accompanied by beneficial gut microbial changes in patients with ASUC.
Exclusive enteral nutritionsupplemented corticosteroid therapy in acute severe ulcerative colitis (ASUC) is accompanied by the enrichment of beneficial gut microbial genera, which correlate negatively with the disease activity scores and objective inflammatory markers in ASUC. The baseline gut microbiota in ASUC associates with and may predict corticosteroid response.
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Colitis Ulcerosa , Enfermedad de Crohn , Microbioma Gastrointestinal , Humanos , Enfermedad de Crohn/terapia , Nutrición Enteral , Colitis Ulcerosa/tratamiento farmacológico , Bacterias , Corticoesteroides/uso terapéutico , Inducción de RemisiónRESUMEN
BACKGROUND: Precise estimates of placebo response rates help efficient clinical trial design. In this systematic review and meta-analysis, we assessed contemporary placebo endoscopic and histological response rates in Crohn's disease (CD) clinical trials. METHODS: MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to April 2022 to identify placebo-controlled studies of pharmacological interventions for CD. Endoscopic response, remission, and mucosal healing rates for participants assigned to placebo in induction and maintenance studies were pooled using a random-effects model. Point estimates and associated 95% confidence intervals (CIs) were calculated. RESULTS: In total, 16 studies (11 induction, 3 maintenance, 2 induction and maintenance) that randomized 1646 participants to placebo were eligible. For induction trials, the pooled placebo endoscopic response, endoscopic remission, and mucosal healing rates in participants assigned to placebo were 13% (95% CI, 10-16; I2â =â 14.1%; P = .14), 6% (95% CI, 3-11; I2â =â 74.7%; P < .001), and 6% (95% CI, 4-9; I2â =â 26.9%; P = .29), respectively. The pooled endoscopic remission rate in patients who were bio-naïve was 10% (95% CI, 4-23) compared with only 4% (95% CI, 3-7) in bio-experienced patients. For maintenance trials, the pooled endoscopic response, remission, and mucosal healing rates were 7% (95% CI, 1-31; I2â =â 78.2%; P = .004), 11% (95% CI, 4-27; I2â =â 70.8%; P = .06), and 7% (95% CI, 3-15; I2â =â 29.7; P = .23), respectively. Only 3 trials assessed histological outcomes. CONCLUSIONS: Endoscopic placebo rates vary according to trial phase and prior biologic exposure. These contemporary data will serve to inform CD trial design, sample size calculation, and end point selection for future trials.
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Enfermedad de Crohn , Humanos , Enfermedad de Crohn/tratamiento farmacológico , Endoscopía , Inducción de Remisión , Efecto Placebo , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Background and Aims: There are no prospective studies evaluating effect of non-alcoholic fatty liver disease (NAFLD) in patients with ulcerative colitis (UC). This prospective observational study assessed the prevalence of NAFLD, its predictors, and its effect on long-term outcomes in UC. Methods: Consecutive UC patients underwent transient elastography, body composition analysis, bone densitometry, anthropometry, and baseline demographic and subjective global assessment. NAFLD was diagnosed by controlled attenuation parameter of >260 dB/m. To evaluate predictors and outcomes, patients of UC with NAFLD (n = 29) were compared with age- and sex-matched patients of UC without NAFLD (n = 27). Results: Among 107 patients of UC (mean age-29 ± 10.6 years; males = 56%, median disease duration-48 [interquartile range: 24-84] months, left sided/pancolitis = 84%), 27% (n = 29) had NAFLD. Patients with body mass index (BMI) > 23 kg/m2 had higher proportion of NAFLD than with normal or low BMI (54.7% [23/42] vs 10% [5/50] vs 6.7% [1/15]). Patients with NAFLD had high BMI (P < 0.001), waist circumference, and fat mass (P < 0.001) but similar fat-free mass (P = 0.798) compared to patients without NAFLD. There was no difference in immunosuppressant and cumulative steroid exposure between two groups. Dietary parameters including daily energy, protein, fat, and carbohydrate intake were similar between the two groups. On multivariate analysis, high BMI was found to be predictive and low socioeconomic status as a protective factor of NAFLD. On long-term follow-up of three years, there was no difference in steroid, or biologic requirement, disease-related hospitalization, or composite of all three outcomes between two groups. Conclusion: The prevalence of NAFLD was found in nearly a quarter of patients of UC and was affected by metabolic parameters rather than disease activity.
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INTRODUCTION: 30-40% patients with acute severe ulcerative colitis (ASUC) fail intravenous (IV) steroids requiring medical rescue therapy/colectomy. Low baseline albumin predicts steroid non-response, and exclusive enteral nutrition (EEN) has been shown to improve steroid response and albumin levels. Albumin infusion due to its anti-inflammatory and anti-oxidant properties might further improve steroid response in ASUC, which was evaluated in present study. METHODS: In this open-label randomized controlled trial, patients with ASUC were randomized in 1:1 ratio to albumin + standard of care (SOC) + EEN vs. SOC + EEN (Jan2021 - Feb2023). Both arms received 5 days of EEN with 400 mg IV hydrocortisone/day. Patients in albumin arm were administered 5 days of 20% w/v intravenous albumin (100 ml). Primary outcome was 1) steroid failure (need for rescue medical therapy or colectomy) and 2) proportion of patients with adverse events. RESULTS: Sixty-one patients (albumin-30, SOC-31)(mean age-31.6±0.4 years, male-57.4%), were included. Baseline characteristics were comparable. There was no difference in steroid failure between albumin and SOC arm(10/30(33.33 %) vs 13/31(41.94 %), p=0.49). No adverse events were reported with albumin infusions. Colectomy rate(10% vs 9.68%, P=1), response to salvage medical therapy (88.89% vs 76.92%, P=0.62) and median duration of hospitalization (10.5(7-16) vs 10(7-20), P=0.43) were also comparable. Long-term composite outcome of colectomy and re-admission rates was numerically higher in the albumin than SOC arm (37.04% vs 17.86%, p>0.05), although it did not reach statistical significance. CONCLUSION: There was no benefit of intravenous albumin infusion as an adjunct to IV steroids and EEN in patients with ASUC.
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Simultaneous occurrence of multiple sclerosis (MS) and ulcerative colitis (UC) is seldom encountered by clinicians and poses unique challenges. The sphingosine-1-phosphate receptor modulator ozanimod has been recently approved for UC. Ozanimod can be used in such scenarios where it can treat both conditions, reducing the need for multiple targeted therapies. We report the first case of successfully treated multiple sclerosis and UC with ozanimod.
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Inflammatory bowel disease, including Crohn's disease and ulcerative colitis, comprises multiple complex immune-mediated disorders. Early diagnosis and prompt disease control may prevent long-term complications and hospitalization. The therapeutic options have expanded in the last two decades, with the development of biologics and small molecules targeting specific pathways implicated in inflammatory bowel disease pathogenesis. The interleukin (IL)-23/Th-17 axis is one such example. Targeting IL-12/23 is effective for the treatment of both moderate-to-severe Crohn's disease and ulcerative colitis, and ustekinumab (an IL-12/23p40 antagonist) is approved for both indications. In patients with psoriasis, improved clinical outcomes were observed with agents that more selectively targeted IL-23 (IL-23p19 antagonists) compared with those that target both IL-12 and IL-23. Many specific IL-23p19 antagonists are currently being investigated in Crohn's disease and ulcerative colitis, and risankizumab has been recently approved for moderate-to-severely active Crohn's disease. In this review, we summarize the mechanisms of action and the evidence from clinical trials supporting the efficacy and safety of IL-23p19 antagonists for the treatment of inflammatory bowel disease.
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Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Enfermedad de Crohn/tratamiento farmacológico , Interleucina-23 , Colitis Ulcerosa/tratamiento farmacológico , Subunidad p19 de la Interleucina-23 , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Interleucina-12/uso terapéuticoRESUMEN
BACKGROUND: Fistulas are a debilitating complication of Crohn's disease (CD). We conducted a systematic review to assess the efficacy of medical therapies for fistulising CD. METHODS: MEDLINE, Embase, and CENTRAL were searched on May 26, 2022, for randomised controlled trials (RCTs) of pharmacologic therapy in adults with fistulising CD. The primary outcome was induction and maintenance of fistula response. Pooled risk ratios (RRs) and 95% confidence intervals (CI) were calculated. GRADE was used to assess certainty of evidence. RESULTS: Thirty-eight RCTs were included. Nineteen trials (50%) exclusively involved perianal fistula. The remaining studies included some participants with non-perianal fistula. Pooled RRs for anti-tumor necrosis factor (TNF) agents were not statistically significant for induction (RR 1.36, 95% CI 0.97-1.91) or maintenance of fistula response (RR 1.48, 95% CI 0.97-2.27). However, in a sensitivity analysis of studies with fistula response as the primary outcome, anti-TNFs were superior to placebo for induction (RR 1.94, 95% CI 1.10-3.41) and maintenance (RR 1.88, 95% CI 1.23-2.88) of fistula response. Oral small molecules (RR 2.56, 95% CI 1.18-5.53) and mesenchymal stem cell (MSC) therapy (RR 1.26, 95% CI 1.01-1.57) were effective for induction of fistula response. Ustekinumab was associated with maintenance of fistula response (RR 1.80, 95% CI1.04-3.11). Vedolizumab was not superior to placebo. The certainty of evidence ranged from very low to moderate. CONCLUSION: Very low-to-moderate certainty evidence suggests that anti-TNF therapy, oral small molecules, ustekinumab, and MSCs are effective for perianal fistulising CD. Dedicated fistula studies evaluating biologics and small molecules are needed.
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BACKGROUND: This systematic review was performed to characterize the landscape of research conducted in patients with intestinal stoma (IS) and highlight unmet needs for clinical research in Crohn's disease (CD) and IS. METHODS: We searched ClinicalTrials.gov from inception to May 25, 2022, to identify clinical trials assessing interventions in patients with an IS, as well as those with an IS and CD. Studies were grouped according to type of intervention. We excluded observational studies with no treatment arm. RESULTS: A total of 253 studies were included in the final analysis. Most studies investigated devices (nâ =â 122 [48.2%]), or surgical procedures (nâ =â 63 [24.9%]), followed by behavioral interventions (nâ =â 30 [11.8%]), drugs (nâ =â 20 [7.9%]), dietary interventions (nâ =â 2 [0.8%]), skin care products (nâ =â 2 0.8%]), and others (nâ =â 14 [5.5%]). A total of 50.9% (nâ =â 129) of studies had completed recruitment, enrolling 11â 116 participants. Only 6 studies (surgery: nâ =â 3; physiological studies: nâ =â 2; drugs: nâ =â 1) exclusively included patients with inflammatory bowel disease (IBD), and 16 studies commented that patients with IBD were excluded in their eligibility criteria. No study assessed efficacy of drugs in patients with CD and IS. Approximately one-quarter of studies (n = 65 of 253) included quality of life as an outcome measure. CONCLUSION: There is a paucity of research in IBD patients with IS, with the majority focusing on devices and surgical procedures. There have been no drug trials evaluating efficacy in patients with CD and IS. There is an urgent need to identify barriers to enrollment and develop eligibility and outcome measures that enable the inclusion of patients with CD with stoma into clinical trials.
We analyzed registered trials for patients with intestinal stoma with special focus on Crohn's disease patients to explore research and unmet needs. Our results indicate a scarcity of studies in this area with most studies limited to surgical procedures and devices.
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BACKGROUND/AIMS: Intestinal tuberculosis (ITB) and Crohn's disease (CD) frequently present with a diagnostic dilemma because of similar presentation. Interferon-gamma release assay (IGRA) has been used in differentiating ITB from CD, but with sparse reports on its diagnostic accuracy in tuberculosis endemic regions and this study evaluated the same. METHODS: Patients with definitive diagnosis of ITB (n=59) or CD (n=49) who underwent IGRA testing (n=307) were retrospectively included at All India Institute of Medical Sciences, New Delhi (July 2014 to September 2021). CD or ITB was diagnosed as per standard criteria. IGRA was considered positive at >0.35 IU/mL. Relevant data was collected and IGRA results were compared between ITB and CD to determine its accuracy. RESULTS: Among 59 ITB patients (mean age, 32.6±13.1 years; median disease duration, 1 year; male, 59.3%), 24 were positive and 35 tested negative for IGRA. Among 49 CD patients (mean age, 37.8±14.0; median disease duration, 4 years; male, 61.2%), 12 were positive and 37 tested negative for IGRA. Hence, for diagnosing ITB, IGRA showed a sensitivity, specificity, positive and negative predictive values of 40.68%, 75.51%, 66.67%, and 51.39%, respectively. The area under the curve of IGRA for ITB diagnosis was 0.66 (95% confidence interval, 0.55-0.75). In a subset (n=64), tuberculin skin test (TST) showed sensitivity, specificity, positive and negative predictive values of 64.7%, 73.3%, 73.3%, and 64.71%, respectively. IGRA and TST were concordant in 38 (59.4%) patients with κ=0.17. CONCLUSIONS: In a tuberculosis endemic region, IGRA had poor diagnostic accuracy for differentiating ITB from CD, suggesting a limited value of IGRA in this setting.
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BACKGROUND: Ulcerative proctitis (UP) is a common highly symptomatic form of ulcerative colitis that can be difficult to treat. AIM: To assess the efficacy of medical treatments for UP. METHODS: We searched MEDLINE, EMBASE, and CENTRAL on 23 November 2022 for randomised controlled trials (RCTs) of medical therapy for adults with UP. Primary outcomes included induction and maintenance of clinical remission. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for each outcome. RESULTS: We included 53 RCTs (n = 4096) including 46 induction studies (n = 3731) and seven maintenance studies (n = 365). First-line therapies included topical 5-aminosalicylic acid (5-ASA), conventional corticosteroids, budesonide, and oral 5-ASA. Therapy for refractory UP included topical tacrolimus and small molecules. Topical 5-ASA was superior to placebo for induction (RR 2.72, 95% CI 1.94-3.82) and maintenance of remission (RR 2.09, 95% CI 1.26-3.46). Topical corticosteroids were superior to placebo for induction of remission (RR 2.83, 95% CI 1.62-4.92). Topical budesonide was superior to placebo for induction of remission (RR 2.34, 95% CI 1.44-3.81). Combination therapy with topical 5-ASA and topical corticosteroids was superior to topical monotherapy with either agent. Topical tacrolimus was superior to placebo. Etrasimod was superior to placebo for induction (RR 4.71, 95% CI 1.2-18.49) and maintenance of remission (RR 2.08, 95% CI 1.31-3.32). CONCLUSIONS: Topical 5-ASA and corticosteroids are effective for active UP. Topical 5-ASA may be effective for maintenance of remission. Tacrolimus may be effective for induction of remission. Etrasimod may be effective for induction and for maintenance of remission. Trials should include UP to expand the evidence base for this under-represented population.
Asunto(s)
Colitis Ulcerosa , Proctitis , Adulto , Humanos , Administración Oral , Antiinflamatorios no Esteroideos/uso terapéutico , Budesonida/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Mesalamina/uso terapéutico , Proctitis/tratamiento farmacológico , Inducción de Remisión , Tacrolimus/uso terapéuticoRESUMEN
BACKGROUND AND AIMS: Oral small-molecule drugs [SMDs] are expanding the therapeutic landscape for inflammatory bowel disease [IBD]. This systematic review and meta-analysis summarizes the efficacy and safety of JAK inhibitor [JAKi] and sphingosine-1-phosphate [S1P] receptor modulator treatments for ulcerative colitis [UC] and Crohn's disease [CD]. METHODS: MEDLINE, Embase, and CENTRAL were searched from inception to May 30, 2022. Randomized controlled trials [RCTs] of JAKi and S1P receptor modulators in adults with UC or CD were eligible. Clinical, endoscopic, histological, and safety data were pooled and analysed using a random-effects model. RESULTS: Thirty-five RCTs [26 UC, nine CD] were included. In UC, JAKi therapy was associated with induction of clinical (risk ratio [RR] 3.16, 95% confidence interval [CI] 2.03-4.92; I2â =â 65%) and endoscopic [RR 3.99, 95% CI 2.36-6.75; I2â =â 36%] remission compared to placebo. Upadacitinib was associated with histological response [RR 2.63, 95% CI 1.97-3.53]. S1P modulator therapy was associated with induction of clinical [RR 2.52, 95% CI 1.88-3.39; I2â =â 1%] and endoscopic [RR 2.39, 95% CI 1.07-5.33; I2â =â 0%] remission relative to placebo. Ozanimod was superior to placebo for inducing histological remission in UC [RR 2.20, 95% CI 1.43-3.37; I2â =â 0%], while etrasimod was not [RR 2.36, 95% CI 0.71-7.88; I2â =â 0%]. In CD, JAKi therapy was superior to placebo for induction of clinical remission [RR 1.53, 95% CI 1.19-1.98; I2â =â 31%], and endoscopic remission [RR 4.78, 95% CI 1.63-14.06; I2â =â 43%] compared to placebo. The risk of serious infections was similar for oral SMDs and placebo. CONCLUSION: JAKi and S1P receptor modulator therapies are effective in IBD for inducing clinical and endoscopic remission and, in some circumstances, histological response.