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1.
Artículo en Inglés | MEDLINE | ID: mdl-39236736

RESUMEN

BACKGROUND: The optimal dosing strategy for infliximab in steroid-refractory acute severe ulcerative colitis (ASUC) is unknown. We compared intensified and standard dose infliximab rescue strategies and explored maintenance therapies following infliximab induction in ASUC. METHODS: In this open-label, multicentre, randomised controlled trial, patients aged 18 years or older from 13 Australian tertiary hospitals with intravenous steroid-refractory ASUC were randomly assigned (1:2) to receive a first dose of 10 mg/kg infliximab or 5 mg/kg infliximab (randomisation 1). Block randomisation was used and stratified by history of thiopurine exposure and study site, with allocation concealment maintained via computer-generated randomisation. Patients in the 10 mg/kg group (intensified induction strategy [IIS]) received a second dose at day 7 or earlier at the time of non-response; all patients in the 5 mg/kg group were re-randomised between day 3 and day 7 (1:1; randomisation 2) to a standard induction strategy (SIS) or accelerated induction strategy (AIS), resulting in three induction groups. Patients in the SIS group received 5 mg/kg infliximab at weeks 0, 2, and 6, with an extra 5 mg/kg dose between day 3 and day 7 if no response. Patients in the AIS group received 5 mg/kg infliximab at weeks 0, 1, and 3, with the week 1 dose increased to 10 mg/kg and given between day 3 and day 7 if no response. The primary outcome was clinical response by day 7 (reduction in Lichtiger score to <10 with a decrease of ≥3 points from baseline, improvement in rectal bleeding, and decreased stool frequency to ≤4 per day). Secondary endpoints assessed outcomes to day 7 and exploratory outcomes compared induction regimens until month 3. From month 3, maintenance therapy was selected based on treatment experience, with use of thiopurine monotherapy, combination infliximab and thiopurine, or infliximab monotherapy, with follow-up as a cohort study up to month 12. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02770040, and is completed. FINDINGS: Between July 20, 2016, and Sept 24, 2021, 138 patients were randomly assigned (63 [46%] female and 75 [54%] male); 46 received a first dose of 10 mg/kg infliximab and 92 received 5 mg/kg infliximab. After randomisation 1, we observed no significant difference in the proportion of patients who had a clinical response by day 7 between the 10 mg/kg and 5 mg/kg groups (30 [65%] of 46 vs 56 [61%] of 92, p=0·62; risk ratio adjusted for thiopurine treatment history, 1·06 [95% CI 0·94-1·20], p=0·32). We found no significant differences in secondary endpoints including time to clinical response or change in Lichtiger score from baseline to day 7. Two patients who received 10 mg/kg infliximab underwent colectomy in the first 7 days compared with no patients in the 5 mg/kg group (p=0·21). Three serious adverse events occurred in three patients in both the 10 mg/kg group and 5 mg/kg group. After randomisation 2, the proportions of patients with clinical response at day 14 (34 [74%] of 46 in the IIS group, 35 [73%] of 48 in the AIS group, and 30 [68%] of 44 in the SIS group, p=0·81), clinical remission at month 3 (23 [50%], 25 [52%], 21 [48%], p=0·92), steroid-free remission at month 3 (19 [41%], 20 [42%], 18 [41%], p=1·0), endoscopic remission at month 3 (21 [46%], 22 [46%], 21 [48%], p=0·98), and colectomy at month 3 (three [7%] of 45, nine [19%] of 47, five [12%] of 43, p=0·20) were not significantly different between groups. Between day 8 and month 3, the proportion of patients with at least one infectious adverse event possibly related to infliximab was two (4%) of 46 in the IIS group, eight (17%) of 48 in the AIS group, and eight (18%) of 44 in the SIS group (p=0·082). No deaths occurred in the study. INTERPRETATION: Infliximab is a safe and effective rescue therapy in ASUC. In steroid-refractory ASUC, a first dose of 10 mg/kg infliximab was not superior to 5 mg/kg infliximab in achieving clinical response by day 7. Intensified, accelerated, and standard induction regimens did not result in a significant difference in clinical response by day 14 or in remission or colectomy rates by month 3. FUNDING: Australian National Health and Medical Research Council, Gastroenterology Society of Australia, Gandel Philanthropy, Australian Postgraduate Award, Janssen-Cilag.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39209200

RESUMEN

BACKGROUND & AIMS: Intestinal ultrasound (IUS) is increasingly used to assess Crohn's disease (CD) activity in clinical practice. However, application in clinical trials has been limited by heterogeneous scoring methods and concerns about reliability. We aimed to determine the inter- and intra-rater reliability of locally- and centrally-read IUS parameters for evaluating CD using prospectively performed scans. METHODS: Twenty-four participants with CD and 6 gastroenterologists participated in a 2-day workshop where each participant underwent 6 IUS scans in total. Eight IUS parameters (bowel wall thickness [BWT], bowel wall stratification [BWS], color Doppler signal [CDS], inflammatory mesenteric fat [i-fat], submucosal prominence, submucosal layer thickness, haustra coli/peristalsis, and affected segment length) and an overall measure of sonographic disease activity were blindly assessed by the 6 local readers and 4 central gastroenterologist-sonographers. Reliability was quantified using intraclass correlation coefficients (ICCs). Institutional review board approval was granted for this study (12938). RESULTS: Five IUS parameters demonstrated at least moderate (ICC >0.41) inter- and intra-rater reliability when local and central reading was performed (BWT, CDS, i-fat, submucosal prominence, and affected segment length). Reliability was generally better with central, in distinction to local, reading. ICCs for BWS and i-fat were highest when evaluated as binary outcomes. Sensitivity analyses demonstrated that IUS parameters are most reliable when evaluated in the worst affected segment. Fair reliability was observed when local readers identified the worst affected segment. CONCLUSIONS: Local and central reading of IUS demonstrated at least moderate inter- and intra-rater reliability for several parameters. This study supports refining existing activity indices and incorporating IUS central reading into clinical trials.

4.
BMJ Open ; 14(7): e081787, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39032928

RESUMEN

INTRODUCTION: A substantial proportion of patients with inflammatory bowel disease (IBD) on intravenous infliximab require dose intensification. Accessing additional intravenous infliximab is labour-intensive and expensive, depending on insurance and pharmaceutical reimbursement. Observational data suggest that subcutaneous infliximab may offer a convenient and safe alternative to maintain disease remission in patients requiring dose-intensified infliximab. A prospective, controlled trial is required to confirm that subcutaneous infliximab is as effective as dose-intensified intravenous infliximab, to identify predictors of disease flare and to establish the role of subcutaneous infliximab therapeutic drug monitoring. METHODS AND ANALYSIS: The DISCUS-IBD trial is an investigator-initiated, prospective, multicentre, randomised, open-label non-inferiority study comparing the rate of disease flares in participants randomised to continue dose-intensified intravenous infliximab to those switched to subcutaneous infliximab after 48 weeks. Participants are adult patients with IBD in sustained corticosteroid-free remission on any regimen of dose-intensified infliximab up to a maximum of 10 mg/kg 4-weekly intravenously. Participants allocated to intravenous infliximab will continue infliximab at the same dose-intensified regimen they were receiving at study enrolment. Subcutaneous infliximab dosing will be stratified by prior intravenous infliximab dosing. Clinical (Harvey-Bradshaw Index, partial Mayo score), biochemical (C reactive protein, faecal calprotectin), pharmacokinetic (drug-level±antidrug antibodies) and qualitative data are collected 12-weekly until study conclusion at week 48. 13 sites across Australia will participate in recruitment to reach a calculated sample size of 120 participants. ETHICS AND DISSEMINATION: Multisite ethics approval was obtained from the Health District Human Research Ethics Committee (HREC) at The Alfred Hospital under a National Mutual Acceptance (NMA) agreement (HREC/90559/Alfred-2022; Local Reference: Project 618/22, version 1.6, 2 March 2023). Findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals. DISCUS-IBD was prospectively registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR) prior to commencing recruitment. TRIAL REGISTRATION NUMBER: ACTRN12622001458729.


Asunto(s)
Fármacos Gastrointestinales , Enfermedades Inflamatorias del Intestino , Infliximab , Adulto , Femenino , Humanos , Masculino , Administración Intravenosa , Australia , Monitoreo de Drogas/métodos , Fármacos Gastrointestinales/administración & dosificación , Fármacos Gastrointestinales/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab/administración & dosificación , Infliximab/uso terapéutico , Infliximab/farmacocinética , Inyecciones Subcutáneas , Estudios Multicéntricos como Asunto , Estudios Prospectivos
5.
Knee Surg Sports Traumatol Arthrosc ; 32(9): 2258-2266, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38751089

RESUMEN

PURPOSE: To compare short-term patient-reported outcomes (PRO) of two contemporary matrix-associated autologous chondrocyte implantation (M-ACI) products for the treatment of large articular cartilage defects of the knee. METHODS: A retrospective, registry-based, matched-pair analysis was performed, comparing PRO of patients undergoing isolated M-ACI with either Spherox™, a spheroid-based ACI (Sb-ACI), or NOVOCART™ Inject, a hydrogel-based ACI product (Hb-ACI), for a focal full-thickness cartilage defect of the knee ≥4 cm2. Matching parameters included age, sex, body mass index, defect size, defect localization, symptom duration and previous surgeries. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee (IKDC) score were obtained up to the 24-month follow-up. The total KOOS response rate and percentage of patients attaining a substantial clinical benefit (SCB) in KOOS subscores were calculated. RESULTS: A total of 45 patients per group were matched. The response rate after 24 months was not significantly different between the groups (Sb-ACI 64.4% vs. Hb-ACI 82.2%, p = 0.057). The number of patients with a SCB at 24 months was not significantly different in any KOOS subscore, despite significantly higher improvement of the total KOOS (14.8 ± 16.2 vs. 21.5 ± 15.4, p = 0.047) and KOOS pain in the Hb-ACI group (12.2 ± 18.6 vs. 20.6 ± 19.1, p = 0.037). The IKDC score in the Hb-ACI group was significantly higher at the 12- and 24-month follow-up (60.7 ± 20.2 vs. 70.9 ± 18.0, p = 0.013). CONCLUSION: The response rate and number of patients achieving an SCB were not significantly different between patients treated with Sb-ACI or Hb-ACI. Both procedures can achieve favourable 2-year PRO. Hb-ACI was associated with better PRO between 1 and 2 years postoperatively; however, the clinical relevance of this benefit is yet to be proven. LEVEL OF EVIDENCE: III, Retrospective comparative study.


Asunto(s)
Cartílago Articular , Condrocitos , Hidrogeles , Sistema de Registros , Trasplante Autólogo , Humanos , Femenino , Masculino , Estudios Retrospectivos , Adulto , Condrocitos/trasplante , Cartílago Articular/cirugía , Cartílago Articular/lesiones , Persona de Mediana Edad , Alemania , Resultado del Tratamiento , Medición de Resultados Informados por el Paciente , Articulación de la Rodilla/cirugía , Análisis por Apareamiento
6.
Intern Med J ; 54(6): 861-870, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38717051

RESUMEN

There are wide-ranging probiotic choices in Australasia. We reviewed the efficacy of probiotics for the management of gastrointestinal (GI) conditions in adults and assessed relevance to clinical practice. The benefits of probiotics were inconsistent, with a strong consensus reached for only a few of the indications. As different species/strains and combinations differ in efficacy, results cannot be extrapolated from one to another. This review endorses specific probiotics for limited indications. Efficacy of most marketed probiotic formulations remains unstudied and unproven, warranting further research.


Asunto(s)
Enfermedades Gastrointestinales , Probióticos , Probióticos/uso terapéutico , Humanos , Enfermedades Gastrointestinales/terapia , Resultado del Tratamiento
7.
ACG Case Rep J ; 11(3): e01302, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38469431

RESUMEN

The role of antibiotics in the treatment of ulcerative colitis is limited. We present a case of a 25-year-old woman who presented with a flare of ulcerative colitis after an episode of infectious gastroenteritis on a background of known primary sclerosing cholangitis. After the flare, she experienced persistent abdominal pain and diarrhea associated with elevated fecal calprotectin and deep rectosigmoid ulcerations on endoscopy. After unsuccessful trials of vedolizumab, infliximab, and tofacitinib, the patient was commenced on ustekinumab, tacrolimus, and oral vancomycin. Tacrolimus was ceased successfully, but while on maintenance ustekinumab therapy, 2 attempts to cease vancomycin resulted in symptom recurrence and rising fecal calprotectin that improved with vancomycin recommencement. To date, the patient has been on vancomycin continuously for 18 months and remains clinically well with colonoscopy demonstrating inactive colitis. This case highlights how vancomycin may be beneficial in the management of treatment-refractory ulcerative colitis as an adjunct to biologic therapy.

9.
Artículo en Inglés | MEDLINE | ID: mdl-38492905

RESUMEN

BACKGROUND & AIMS: Vedolizumab and ustekinumab pharmacokinetics in pregnancy and the infant after in utero exposure remain incompletely defined. We aim to define the antenatal stability of ustekinumab and vedolizumab levels and the time at which infant drug levels become undetectable. METHODS: This multicenter prospective observational cohort study recruited pregnant or preconception women with inflammatory bowel disease receiving vedolizumab or ustekinumab. Trough drug levels, clinical data, and biochemical data were documented preconception, during each trimester of pregnancy, and postpartum. Maternal and cord blood drug levels were measured at delivery and in infants until undetectable. Infant outcomes were assessed until 2 years of age. RESULTS: A total of 102 participants (vedolizumab, n = 58) were included. The majority of mothers were, and remained, in clinical and biochemical remission. Maternal vedolizumab levels decreased over the course of pregnancy in association with increasing weight, rather than increasing gestation. Maternal ustekinumab levels remained stable. The median time to drug becoming undetectable in the infant was shorter for vedolizumab (11 wk; range, 5-19 wk; n = 32) than ustekinumab (14 wk; range, 9-36 wk; n = 17) and correlated positively with infant delivery level. Thirty-two of 41 (88%) and 17 of 30 (67%) vedolizumab- and ustekinumab-exposed infants had undetectable drug levels by 15 weeks of age, respectively. Pregnancy and infant outcomes were favorable. Twenty infants with undetectable drug levels received the rotavirus vaccine, with no adverse reactions reported. CONCLUSIONS: Maternal vedolizumab levels decreased, whereas ustekinumab levels remained stable over the course of pregnancy. Most vedolizumab- and approximately half of ustekinumab-exposed infants had undetectable drug levels by 15 weeks of age. No concerning maternal or infant safety signals were identified.

10.
Front Immunol ; 15: 1342477, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38476237

RESUMEN

Introduction: We evaluated baseline Clearance of anti-tumor necrosis factors and human leukocyte antigen variant (HLA DQA1*05) in combination as poor prognostic factors (PPF) of pharmacokinetic (PK) origin impacting immune response (formation of antidrug antibodies) and disease control of inflammatory bowel disease (IBD) patients treated with infliximab or adalimumab. Methods: Baseline Clearance was estimated in IBD patients before starting treatment using weight and serum albumin concentrations. HLA DQA1*05 carrier status (rs2097432 A/G or G/G variant) was measured using real time polymerase chain reaction. The outcomes consisted of immune response, clinical and biochemical remission (C-reactive protein<3 mg/L in the absence of symptoms), and endoscopic remission (SES-CD<3). Statistical analysis consisted of logistic regression and nonlinear mixed effect models. Results and discussion: In 415 patients enrolled from 4 different cohorts (median age 27 [IQR: 15-43] years, 46% females), Clearance>0.326 L/day and HLA DQA1*05 carrier status were 2-fold more likely to have antidrug antibodies (OR=2.3, 95%CI: 1.7-3.4; p<0.001, and OR=1.9, 95%CI: 1.4-2.8; p<0.001, respectively). Overall, each incremental PPF of PK origin resulted in a 2-fold (OR=2.16, 95%CI: 1.7-2.7; p<0.11) [corrected] higher likelihood of antidrug antibody formation. The presence of both PPF of PK origin resulted in higher rates of antidrug antibodies (p<0.01) and lower clinical and biochemical remission (p<0.01). Each incremental increase in PPF of PK origin associated with lower likelihood of endoscopic remission (OR=0.4, 95%CI: 0.2-0.7; p<0.001). Prior biologic experience heightened the negative impact of PPF of PK origin on clinical and biochemical remission (p<0.01). Implementation of proactive therapeutic drug monitoring reduced it, particularly during maintenance and in the presence of higher drug concentrations (p<0.001). We conclude that PPF of PK origin, including both higher Clearance and carriage of HLA DQA1*05, impact outcomes in patients with IBD.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Femenino , Humanos , Adulto , Masculino , Pronóstico , Adalimumab/uso terapéutico , Infliximab/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/uso terapéutico , Anticuerpos , Necrosis/tratamiento farmacológico
11.
J Crohns Colitis ; 18(2): 212-222, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-37594369

RESUMEN

OBJECTIVE: We postulated that adalimumab [ADA] drug clearance [CL] may be a more critical determinant of therapeutic outcome than ADA concentration. This was tested in Crohn's disease [CD] patients undergoing ADA maintenance treatment. METHODS: CD patients from four cohorts received ADA induction and started maintenance therapy. Therapeutic outcomes consisted of endoscopic remission [ER], sustained C-reactive protein [CRP] based clinical remission [defined as CRP levels below 3 mg/L in the absence of symptoms], and faecal calprotectin [FC] level below 100 µg/g. Serum albumin, ADA concentration, and anti-drug antibody status were determined using immunochemistry and homogeneous mobility shift assay, respectively. CL was determined using a nonlinear mixed effect model with Bayesian priors. Statistical analysis consisted of Mann-Whitney test and logistic regression with calculation of odds ratio. Repeated event analysis was conducted using a nonlinear mixed effect model. RESULTS: In 237 enrolled patients [median age 40 years, 45% females], median CL was lower in patients achieving ER as compared with those with persistent active endoscopic disease [median 0.247 L/day vs 0.326 L/day, respectively] [p <0.01]. There was no significant difference in ADA concentration between patients in endoscopic remission compared with those with recurrence [median 9.3 µg/mL vs 11.7 µg/mL, respectively]. Sustained CRP-based clinical remission and FC levels below 100 µg/g were generally associated with lower CL and higher ADA concentration. Repeated event analysis confirmed those findings with better performances of CL than concentration in associating with ER and other outcomes. CONCLUSION: Lower ADA clearance is associated with an improved clinical outcome for patients with Crohn's disease and may be a superior pharmacokinetic measure than concentration.


Asunto(s)
Adalimumab , Enfermedad de Crohn , Adulto , Femenino , Humanos , Masculino , Adalimumab/uso terapéutico , Anticuerpos , Teorema de Bayes , Proteína C-Reactiva/metabolismo , Enfermedad de Crohn/tratamiento farmacológico , Inducción de Remisión , Resultado del Tratamiento
12.
J Am Coll Radiol ; 21(3): 441-463, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37852561

RESUMEN

PURPOSE: Cross-sectional imaging facilitates the assessment of transmural healing in patients with Crohn's disease. This systematic review addresses the utility of MRI and intestinal ultrasound (IUS) in the assessment of disease activity in response to drug therapy compared with endoscopy in patients with luminal Crohn's disease. METHODS: Database searches were undertaken using predefined terms. Studies with ≥10 patients with luminal Crohn's disease with paired endoscopy and imaging (MRI or IUS) after treatment initiation were included. Publications were identified through searches of six bibliographic databases, all run on June 24, 2022. Records were screened on title and abstract, then full text, by two independent reviewers. RESULTS: In total, 5,760 records were identified, with 24 studies meeting the inclusion criteria. Ten studies examined IUS and found good correlation between IUS and endoscopic remission (κ = 0.63-0.73). Early reduction in bowel wall thickness at 4 to 8 weeks predicted endoscopic response at 12 to 38 weeks (area under the receiver operating characteristic curve [AUROC], 0.77; odds ratio, 10.8; P = .01). Twelve studies examined MRI, with the Magnetic Resonance Index of Activity score having high accuracy for predicting endoscopic remission (AUROC, 0.97; sensitivity, 93%; specificity, 77%). A Simplified Magnetic Resonance Index of Activity score cutoff of ≥1 identifies active endoscopic disease (AUROC, 0.92; 95% confidence interval, 0.88-0.95; P < .0001). CONCLUSIONS: IUS and MRI are both reliable, noninvasive modalities for assessing transmural healing in patients with Crohn's disease and are accurate in monitoring the response to drug therapy. These modalities can be used to monitor response to biologic induction therapy, with early changes predictive of response to treatment.


Asunto(s)
Enfermedad de Crohn , Humanos , Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/tratamiento farmacológico , Imagen por Resonancia Magnética , Endoscopía Gastrointestinal/métodos , Curva ROC
13.
ANZ J Surg ; 93(6): 1503-1509, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37095321

RESUMEN

BACKGROUND: In medically refractory Ulcerative Colitis (UC), proctocolectomy with ileoanal pouch procedure (IAPP) is the preferred continence-preserving surgical option. Functional outcomes post-surgery and long-term complication rates in the biologic era remain ambiguous. This review primarily aims to provide an update on these outcomes. Secondarily, risk factors associated with chronic pouchitis and pouch failure are explored. METHODS: Two online databases (MEDLINE and EMBASE) were searched on 4 October 2022 for English studies from 2011-present relating to long-term outcomes of IAPP in inflammatory bowel disease (IBD) patients. Adult patients with 12 month follow-up were included. Studies focused on 30-day post-operative outcomes, non-IBD patients or studies including less than 30 patients were excluded. RESULTS: Following screening and full-text review of 1094 studies, 49 were included. Median sample size was n = 282 (IQR: 116-519). Median incidences for chronic pouchitis and pouch failure were 17.1% (IQR: 12-23.6%) and 6.9% (IQR: 4.8-10.8%), respectively. Upon multivariate analysis, chronic pouchitis development was most significantly associated with pre-operative steroid use, pancolitis and extra-intestinal IBD manifestations, whilst pouch failure was most significantly associated with pre-operative diagnosis of Crohn's disease (compared to UC), peri-operative pelvic sepsis and anastomotic leak. Overall patient satisfaction was very high with four included studies reporting greater than 90% satisfaction rates. CONCLUSION: Long-term complications for IAPP were common. However, despite this, patient satisfaction post-IAPP was high. Up-to-date knowledge of complication rates and their risk factors improves pre-operative counselling, management planning and patient outcomes.


Asunto(s)
Colitis Ulcerosa , Reservorios Cólicos , Enfermedades Inflamatorias del Intestino , Reservoritis , Proctocolectomía Restauradora , Adulto , Humanos , Reservoritis/etiología , Reservoritis/complicaciones , Reservorios Cólicos/efectos adversos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/cirugía , Proctocolectomía Restauradora/efectos adversos , Proctocolectomía Restauradora/métodos , Colitis Ulcerosa/cirugía , Colitis Ulcerosa/complicaciones , Complicaciones Posoperatorias/etiología
14.
Eur J Gastroenterol Hepatol ; 35(5): 609-612, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36966753

RESUMEN

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) remains the preferred surgical option for medically refractory ulcerative colitis. Management of individuals with an IPAA prior to and during pregnancy presents challenges that can have serious consequences. Infertility, mechanical obstructive and inflammatory pouch complications are frequently encountered in pregnant women with an IPAA. Mechanical obstructions occur due to a variety of underlying aetiologies, including stricturing disease, adhesions and pouch twists. Conservative management of such obstructions often results in resolution of symptoms without a need for endoscopic or surgical intervention, although endoscopic decompression may be attempted in isolation or as a bridge to definitive surgical intervention. Parenteral nutrition, and early delivery, may also be necessary. Faecal calprotectin and intestinal ultrasound, both of which are accurate in pregnancy, are useful in the setting of suspected inflammatory pouch complications, in some circumstances allowing for avoidance of pouchoscopy. Penicillin-based antimicrobials can be considered first line in pregnancy for the management of pouchitis and pre-pouch ileitis, and biologics can be safely instituted in the setting of refractory disease or suspected Crohn's disease-like inflammation of the pouch or pre-pouch ileum. Pragmatism, clear patient communication and multidisciplinary discussion are essential in approaching pregnant women with complications of an IPAA, particularly given the lack of definitive evidence to guide therapeutic decisions.


Asunto(s)
Colitis Ulcerosa , Reservorios Cólicos , Reservoritis , Proctocolectomía Restauradora , Embarazo , Humanos , Femenino , Proctocolectomía Restauradora/efectos adversos , Descompresión Quirúrgica/efectos adversos , Vértebras Lumbares , Reservoritis/diagnóstico , Reservoritis/etiología , Reservoritis/terapia , Colitis Ulcerosa/diagnóstico , Anastomosis Quirúrgica/efectos adversos , Fertilidad , Reservorios Cólicos/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapia
15.
Case Rep Gastroenterol ; 17(1): 155-159, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36879582

RESUMEN

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis of small to medium vessels. Gastrointestinal involvement is uncommon and is associated with higher mortality. Treatment is based on empiric evidence. In this article, we report a case of EGPA-related pancolitis and stricturing small bowel disease managed with a combination of mepolizumab and surgical resection.

16.
Cell Mol Gastroenterol Hepatol ; 16(1): 165-181, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36972763

RESUMEN

Autoimmune and inflammatory disorders, including inflammatory bowel disease (IBD), commonly affect women of childbearing age, warranting the use of immunomodulatory agents at a time where pregnancy may be desired. In utero exposure to pro-inflammatory mediators from maternal IBD, IBD-associated intestinal dysbiosis, and immunomodulatory drug use may impact neonatal immune system development during what is considered to be a critical period, with potential long-lasting impacts on susceptibility to disease. Both the innate and adaptative immune systems of the neonatal differ to that of the adult in terms of both cellular composition and sensitivity to antigenic and innate stimulation. The infant immune system gradually develops to more closely resemble that of the adult. Exposure to maternal inflammation in utero may aberrantly impact this period of infant immune system development, with maternal autoimmune and inflammatory disorders shown to affect the physiologic changes in serum cytokine abundance observed during pregnancy. The maternal and neonatal intestinal microbiome greatly influence infant mucosal and peripheral immune system development, and thereby impact the susceptibility to short-term inflammatory diseases, the adequacy of vaccine response, and later life risk of atopic and inflammatory disorders. Maternal disease, mode of delivery, method of feeding, time of weaning to include solid foods in the diet, and neonatal antibiotic exposure all influence the composition of the infant microbiome, and thereby infant immune system maturation. How exposure to specific immunosuppressive medications in utero alters infant immune cell phenotype and response to stimulation has been explored, but with existing studies limited by the time at which samples are performed, heterogenicity in methods, and small sample size. Furthermore, the impact of more recently introduced biologic agents have not been explored. Evolving knowledge in this field may influence therapeutic preferences for individuals with IBD planning to conceive, particularly if substantive differences in the risk of infant infection and childhood immune disease are identified.


Asunto(s)
Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Embarazo , Femenino , Humanos , Factores Inmunológicos/efectos adversos , Citocinas , Inflamación
17.
Eur J Drug Metab Pharmacokinet ; 48(3): 271-279, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36952135

RESUMEN

BACKGROUND AND OBJECTIVES: The role of therapeutic drug monitoring for ustekinumab in the treatment of Crohn's disease has not been defined. This study aimed to explore the relationship of serum ustekinumab trough concentration (UTC) with clinical and biochemical disease outcomes in a real-world setting. METHODS: We performed a retrospective analysis of Crohn's disease patients treated at a single tertiary centre. Ustekinumab was given as a single intravenous induction dose, followed by maintenance subcutaneous injections every 4 to 8 weeks. Rates of clinical remission (Harvey-Bradshaw Index ≤ 4), biochemical remission (C-reactive protein < 5 mg/l and faecal calprotectin < 150 µg/g) and complete remission were assessed at baseline and at the time of UTC testing during maintenance therapy. The association between baseline variables and UTC was tested using linear regression. We also performed an external validation analysis of UTC cut-offs established in four previously published studies. RESULTS: This study included 43 patients. Compared to 8-weekly dosing, a 2.49- and 2.65-fold increase in UTC was associated with 6-weekly and 4-weekly dosing respectively. However, there was no significant difference in clinical, biochemical or complete remission among the dosing groups. An external validation of previously published optimal UTC cut-offs found low predictive value for our patient population. CONCLUSIONS: In this study, dosing interval was the only determinant significantly associated with a higher UTC for patients on maintenance ustekinumab therapy. While a higher UTC may be achieved with dose escalation, it was not associated with improved rates of clinical or biochemical response in our cohort.


Asunto(s)
Enfermedad de Crohn , Ustekinumab , Humanos , Adulto , Ustekinumab/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/metabolismo , Estudios Retrospectivos , Inducción de Remisión , Administración Intravenosa
18.
Aust J Gen Pract ; 51(10): 747-753, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36184855

RESUMEN

BACKGROUND: Inflammatory bowel disease (IBD), comprising ulcerative colitis and Crohn's disease, commonly affects individuals of childbearing age. Pregnancy in women with IBD presents an anxiety-provoking prospect for practitioners and patients alike, with disease flares occurring in between 20% and 55% of patients antenatally. OBJECTIVE: The aim of this review is to provide an overview of antenatal IBD management principles and therapeutic goals, with a specific focus on the role of general practitioners. DISCUSSION: A collaborative approach is favoured in managing pregnancy and IBD. Preconception counselling should be prioritised, with emphasis on the importance of achieving three months of preconception corticosteroid-free remission. Close monitoring of disease activity in pregnancy is crucial, warranting the careful interpretation of both clinical and biochemical parameters. Reassurance regarding the safety of IBD medications in pregnancy and vaginal delivery can be provided in the majority of cases. Specialist support should be sought expeditiously in the setting of disease flare, particularly where symptoms and biochemical parameters are refractory to escalation of 5-aminosalicylates or topical therapies, corticosteroids or biologic agents are required, or an emergent IBD complication is suspected.


Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Corticoesteroides/uso terapéutico , Factores Biológicos/uso terapéutico , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/terapia , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/terapia , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Periodo Posparto , Embarazo
19.
J Crohns Colitis ; 16(12): 1797-1807, 2022 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-35689453

RESUMEN

INTRODUCTION: Crohn's disease recurs after intestinal resection. This study evaluated accuracy of a new blood test, the Endoscopic Healing Index [EHI], in monitoring for disease recurrence. METHODS: Patients enrolled in the prospective POCER study [NCT00989560] underwent a postoperative colonoscopic assessment at 6 [2/3 of patients] and 18 months [all patients] following bowel resection, using the Rutgeerts score [recurrence ≥i2]. Serum was assessed at multiple time points for markers of endoscopic healing using the EHI, and paired with the Rutgeerts endoscopic score as the reference standard. RESULTS: A total of 131 patients provided 437 serum samples, which were paired with endoscopic assessments available in 94 patients [30 with recurrence] at 6 months and 107 patients [44 with recurrence] at 18 months. The median EHI at 6 months was significantly lower in patients in remission [Rutgeerts 

Asunto(s)
Enfermedad de Crohn , Humanos , Biomarcadores/análisis , Colonoscopía , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/cirugía , Heces/química , Íleon/cirugía , Complejo de Antígeno L1 de Leucocito , Estudios Prospectivos , Recurrencia
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