Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.880
Filtrar
2.
Gut ; 69(1): 74-82, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30996042

RESUMO

OBJECTIVE: Over half of patients with IBS have either diarrhoea (IBS-D) or a mixed stool pattern (IBS-M). The relative efficacy of licenced pharmacological therapies is unclear in the absence of head-to-head trials. We conducted a network meta-analysis to resolve this uncertainty. DESIGN: We searched MEDLINE, Embase, Embase Classic, the Cochrane central register of controlled trials, and Clinicaltrials.gov through January 2019 to identify randomised controlled trials (RCTs) assessing the efficacy of licenced pharmacological therapies (alosetron, eluxadoline, ramosetron and rifaximin) in adults with IBS-D or IBS-M. Trials included in the analysis reported a dichotomous assessment of overall response to therapy, and data were pooled using a random effects model. Efficacy and safety of all pharmacological therapies were reported as a pooled relative risk with 95% CIs to summarise the effect of each comparison tested. Treatments were ranked according to their p score. RESULTS: We identified 18 eligible RCTs (seven alosetron, five ramosetron, two rifaximin and four eluxadoline), containing 9844 patients. All were superior to placebo for the treatment of IBS-D or IBS-M at 12 weeks, according to the Food and Drug Administration (FDA)-recommended endpoint for trials in IBS. Alosetron 1 mg twice daily was ranked first for efficacy, based on the FDA-recommended composite endpoint of improvement in both abdominal pain and stool consistency, effect on global symptoms of IBS and effect on stool consistency. Ramosetron 2.5µg once daily was ranked first for effect on abdominal pain. Total numbers of adverse events were significantly greater with alosetron 1 mg twice daily and ramosetron 2.5µg once daily, compared with placebo. Rifaximin 550 mg three times daily ranked first for safety. Constipation was significantly more common with all drugs, except rifaximin 550 mg three times daily. CONCLUSION: In a network meta-analysis of RCTs of pharmacological therapies for IBS-D and IBS-M, we found all drugs to be superior to placebo, but alosetron and ramosetron appeared to be the most effective.


Assuntos
Diarreia/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Síndrome do Intestino Irritável/tratamento farmacológico , Dor Abdominal/tratamento farmacológico , Dor Abdominal/etiologia , Diarreia/etiologia , Determinação de Ponto Final/normas , Fármacos Gastrointestinais/efeitos adversos , Humanos , Síndrome do Intestino Irritável/complicações , Manejo da Dor/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Falha de Tratamento , Resultado do Tratamento
3.
Medicine (Baltimore) ; 98(43): e17652, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651888

RESUMO

RATIONALE: Intestinal Behçet's disease (BD) is characterized by intestinal ulcerations and gastrointestinal symptoms. Ulcerative intestinal tuberculosis (TB) is usually with dyspepsia, abdominal pain, vomiting, and weight loss. The 2 diseases exhibit similar clinical manifestations, but the most critical aspects of their clinical courses and required treatments are not at all similar. PATIENT CONCERNS: We present a case in which a patient with intestinal Behçet's disease developed a de novo ulcerative intestinal TB infection after the start of anti-tumor necrosis factor-α treatment. This was despite histopathologic examination without caseous necrosis granuloma and negative for acid-fast staining and latent TB screen. DIAGNOSES: Intestinal Behçet's disease and intestinal TB. INTERVENTIONS: The patient was treated with quadruple antituberculous chemotherapy, comprising rifapentine, isoniazid, ethambutol, and pyrazinamide. OUTCOMES: At follow-up about 3 months, the therapy of oral antituberculous drugs and thalidomide was continued and the patient's condition had stabilized. LESSONS: This case illustrates the importance of closely monitoring patients who are on infliximab for possible onset of TB, even without abdominal symptoms, and with negative screening results for latent TB.


Assuntos
Síndrome de Behçet/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Infliximab/efeitos adversos , Tuberculose Gastrointestinal/induzido quimicamente , Adulto , Antituberculosos/uso terapêutico , Feminino , Humanos , Tuberculose Gastrointestinal/tratamento farmacológico
4.
Expert Rev Clin Pharmacol ; 12(11): 1019-1026, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31575291

RESUMO

Introduction. Chronic idiopathic constipation (CIC) is a functional gastrointestinal disorder that is associated with an increased healthcare cost and an abnormally poor quality of life. Plecanatide is a natural analog to the peptide agonist of the guanylate cyclase-C (GC-C) receptor, uroguanylin. The conversion of guanosine 5-triphosphate to cyclic guanosine monophosphate results in an increased bowel fluid secretion. Plecanatide is a promising new agent for CIC unresponsive to current therapeutic regimes.Areas covered. A comprehensive online search of Medline and the Science Citation Index was made using the keywords 'plecanatide', 'guanylate cyclase-C agonists', and 'constipation', in various combinations. We reviewed the pharmacodynamics, pharmacokinetics, and metabolism of this agent, and the most significant studies regarding the clinical efficacy and safety of plecanatide in CIC therapy.Expert opinion. Experimental studies showed that plecanatide was significantly better than placebo in reducing CIC severity, straining, stool consistency, bowel movements and quality of life. Apart from limited cases of diarrhea, no serious adverse events were reported. However, few data are available on its long-term safety. Furthermore, patients' affordability of plecanatide can be limited by its costs. Finally, this new agent with a different way of action can be proposed in patients refractory to common therapy.


Assuntos
Constipação Intestinal/tratamento farmacológico , Agonistas da Guanilil Ciclase C/uso terapêutico , Peptídeos Natriuréticos/uso terapêutico , Adulto , Animais , Doença Crônica , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/farmacologia , Fármacos Gastrointestinais/uso terapêutico , Agonistas da Guanilil Ciclase C/efeitos adversos , Agonistas da Guanilil Ciclase C/farmacologia , Humanos , Peptídeos Natriuréticos/efeitos adversos , Peptídeos Natriuréticos/farmacologia , Qualidade de Vida
5.
Gastroenterology ; 157(4): 1019-1031.e7, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31279870

RESUMO

BACKGROUND & AIMS: Although ustekinumab is an effective therapy for moderate to severe Crohn's disease (CD), its effects on the microscopic manifestations of CD are unknown. METHODS: We evaluated the effects of ustekinumab on histologic CD activity in an analysis of data from 251 participants in phase 3 induction and maintenance studies. Two endoscopic biopsy samples were collected at weeks 0, 8, and 44 from the ileum, splenic flexure, and rectum (18 biopsy samples from each patient). Histologic activity was assessed based on global histology activity scores (GHASs). RESULTS: At week 8, the mean GHAS was significantly reduced after ustekinumab induction treatment (from 10.4 ± 7.0 to 7.1 ± 5.9; P < .001) but not in patients who received placebo (from 9.2 ± 6.4 to 7.8 ± 6.2). At week 44 in the randomized maintenance therapy population, the mean GHAS remained reduced from week 8 in patients who received subcutaneous ustekinumab (90 mg every 8 weeks; from 7.4 ± 7.7 to 6.1 ± 4.7) but not every 12 weeks (from 5.3 ± 3.9 to 8.7 ± 4.1) or placebo (from 9.2 ± 3.8 to 10.9 ± 7.1). In the pooled (randomized and nonrandomized) maintenance therapy population, histologic improvement continued in patients given ustekinumab every 8 weeks (from 7.1 ± 6.2 to 5.2 ± 4.2; P < .0001) but not in those given ustekinumab every 12 weeks (from 6.1 ± 5.7 to 7.2 ± 5.1) or placebo (from 8.2 ± 4.2 to 8.9 ± 6.8). A significantly greater proportion of patients achieved histologic response (≥50% decrease in GHAS from baseline) at week 44 if they received ustekinumab every 8 weeks (50% in the randomized maintenance population and 54% in the pooled maintenance population) compared with every 12 weeks (17% and 39% in the randomized and pooled populations, respectively) or placebo (0% and 22% in the randomized and pooled populations, respectively) (P = .0137 for every 8 weeks vs placebo and P = .3529 for every 12 weeks vs placebo in the randomized population; P = .0168 for every 8 weeks vs placebo and P = .3069 for every 12 weeks vs placebo in the pooled population). Regional and overall mean GHASs correlated with the simple endoscopic score for CD (r = .6255, P < .0001). Multivariate analysis found an association between histologic improvement and endoscopic or histologic burden at baseline. CONCLUSIONS: In an analysis of data from participants in phase 3 induction and maintenance trials, we found histologic improvement in a greater proportion of patients given ustekinumab vs placebo. The largest improvements occurred in patients who received ustekinumab maintenance therapy every 8 weeks. ClinicalTrials.gov nos. NCT01369329, NCT01369342, and NCT01369355.


Assuntos
Anti-Inflamatórios/administração & dosagem , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/administração & dosagem , Mucosa Intestinal/efeitos dos fármacos , Ustekinumab/administração & dosagem , Cicatrização/efeitos dos fármacos , Adulto , Anti-Inflamatórios/efeitos adversos , Biópsia , Doença de Crohn/patologia , Esquema de Medicação , Endoscopia Gastrointestinal , Feminino , Fármacos Gastrointestinais/efeitos adversos , Humanos , Quimioterapia de Indução , Mucosa Intestinal/patologia , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento , Ustekinumab/efeitos adversos
6.
Gastroenterology ; 157(4): 1007-1018.e7, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31279871

RESUMO

BACKGROUND & AIMS: Vedolizumab is a gut-selective monoclonal antibody for the treatment of moderately to severely active Crohn's disease (CD). We performed a prospective study of endoscopic, radiologic, and histologic healing in patients with CD who received vedolizumab therapy. METHODS: We performed a phase 3b, open-label, single-group study of 101 patients with at least 3 months of active CD (a CD Activity Index [CDAI] score of 220-450, a simple endoscopic score for CD [SES-CD] of 7 or more, 1 or more mucosal ulcerations [identified by endoscopy], and failure of conventional therapy) from March 2015 through December 2017. Among the patients enrolled, 54.5% had previous failure of 1 or more tumor necrosis factor (TNF) antagonists and 44.6% had severe endoscopic disease activity (SES-CD scores above 15) at baseline. Participants received vedolizumab (300 mg intravenously) at weeks 0, 2, and 6, and then every 8 weeks thereafter, for 26 weeks (primary study) or 52 weeks (substudy, 56 patients). The primary endpoint at week 26 was endoscopic remission (SES-CD score of 4 or less); other endpoints included endoscopic response (50% reduction in SES-CD), radiologic remission (magnetic resonance index of activity score below 7), and histologic response (modified global histologic disease activity score of 4 or less). RESULTS: At week 26, 11.9% of patients were in endoscopic remission (95% confidence interval [CI] 6.3-9.8); at week 52, 17.9% of the patients were in endoscopic remission (95% CI 8.9-30.4). Higher proportions of patients naïve to TNF antagonists achieved endoscopic remission than patients with TNF-antagonist-failure at weeks 26 and 52. Higher proportion of patients with moderate CD (SES-CD scores, 7-15) achieved endoscopic remission at weeks 26 and 52 than patients with severe CD (SES-CD scores above 15). The proportion of patients with complete mucosal healing increased over time, with greater rates of healing in the colon than in the ileum. Remission was detected by magnetic resonance enterography in 21.9% of patients at week 26 (95% CI 9.3-40.0) and in 38.1% at week 52 (95% CI 18.1-61.6). At week 26, 24.4% of patients had a histologic response in the colon (95% CI 15.3-35.4) and 28.3% of patients had a histologic response in the ileum (95% CI 17.5-41.4). At week 52, 20.5% of patients had a histologic response in the colon (95% CI 9.8-35.3) and 34.3% of patients had a histologic response in the ileum (95% CI 19.1-52.2). There were no notable safety issues, including worsening of extraintestinal manifestations. CONCLUSIONS: In a phase 3b trial, we found that 26 and 52 weeks of treatment with vedolizumab (300 mg, at weeks 0, 2, and 6, and then every 8 weeks thereafter) induces endoscopic, radiologic, and histologic healing in patients with moderately to severely active CD. ClinicalTrials.gov no: NCT02425111.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Doença de Crohn/tratamento farmacológico , Endoscopia Gastrointestinal , Fármacos Gastrointestinais/uso terapêutico , Mucosa Intestinal/efeitos dos fármacos , Imagem por Ressonância Magnética , Cicatrização/efeitos dos fármacos , Adulto , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Biópsia , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/patologia , Feminino , Fármacos Gastrointestinais/efeitos adversos , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Qualidade de Vida , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
Gastroenterology ; 157(4): 997-1006.e6, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31175865

RESUMO

BACKGROUND & AIMS: We evaluated the ability of vedolizumab to induce endoscopic and histologic remission in patients with Crohn's disease (CD). METHODS: We performed a prospective study of 110 patients with active CD, based on CD activity index (CDAI) scores >220 and mucosal ulcerations, who received open-label vedolizumab (300 mg) infusions at weeks 0, 2, and 6, and every 8 weeks thereafter through week 52 at tertiary centers in Europe. Patients received an additional infusion at week 10 if their CDAI score had not decreased by 70 points. Patients underwent ileocolonoscopy with collection of biopsies at baseline and weeks 26 and 52; a local and central reader determined simple endoscopic index for CD (SES-CD) scores. Histologic features were assessed by a blinded pathologist at week 26. Serum concentrations of vedolizumab were measured at serial time points. The primary outcome was endoscopic and histologic remission in patients with active CD treated with vedolizumab for 52 weeks. RESULTS: At weeks 26 and 52, 36 patients (29%) and 34 patients (31%), respectively, were in corticosteroid-free clinical remission (CDAI score <150), respectively. Based on intent-to-treat analysis, endoscopic remission (SES-CD score <4) was achieved by 36 patients (33%) and 40 patients (36%) at weeks 26 and 52. Endoscopic responses (decrease in SES-CD score ≥50%) occurred in 44 patients (40%) at week 26 and 5 patients (45%) at week 52. Serum concentrations of vedolizumab were higher at weeks 2, 10, and 22 in patients with lower SES-CD scores. Histologic remission at week 26 was observed in 43 (64%) of 67 patients based on Geboes Score and 37 (66%) of 56 patients based on Robarts Histopathology Index scores in analyses of paired biopsies with inflammation at baseline. Serum concentrations of vedolizumab above 10 mg/L at week 22 were associated with endoscopic remission at week 26. CONCLUSIONS: In a prospective trial, we found that approximately one-third of patients with CD achieve endoscopic remission after 52 weeks of treatment with vedolizumab and two-thirds achieve histologic remission at week 26. Higher serum concentrations of vedolizumab were associated with better outcomes. EUDRACT no: 2014-005376-29.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Doença de Crohn/tratamento farmacológico , Endoscopia Gastrointestinal , Fármacos Gastrointestinais/uso terapêutico , Mucosa Intestinal/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Corticosteroides/uso terapêutico , Adulto , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/sangue , Anti-Inflamatórios/farmacocinética , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/sangue , Anticorpos Monoclonais Humanizados/farmacocinética , Bélgica , Biópsia , Doença de Crohn/sangue , Doença de Crohn/patologia , Monitoramento de Medicamentos , Feminino , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/sangue , Fármacos Gastrointestinais/farmacocinética , Humanos , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Países Baixos , Valor Preditivo dos Testes , Estudos Prospectivos , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento
9.
BMJ Case Rep ; 12(4)2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31036734

RESUMO

We report a 36-year-old man who developed a large epidural and paraspinal abscess as a complication of infliximab therapy being used for underlying Crohn's disease. Cultures of the collection grew methicillin-susceptible Staphylococcus aureus, and treatment consisted of abscess drainage, prolonged intravenous and oral flucloxacillin and temporary withholding of his infliximab. While infection-related complications are well described with infliximab therapy, this is the first description of a large paraspinal abscess with epidural extension.


Assuntos
Abscesso/microbiologia , Doença de Crohn/tratamento farmacológico , Espaço Epidural/microbiologia , Infliximab/efeitos adversos , Abscesso/diagnóstico por imagem , Abscesso/tratamento farmacológico , Abscesso/cirurgia , Adulto , Antibacterianos/uso terapêutico , Anticorpos Monoclonais , Doença de Crohn/complicações , Drenagem/métodos , Espaço Epidural/diagnóstico por imagem , Floxacilina/administração & dosagem , Floxacilina/uso terapêutico , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/uso terapêutico , Humanos , Infliximab/uso terapêutico , Masculino , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/isolamento & purificação , Resultado do Tratamento
10.
Ir Med J ; 3(112): 902, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-31124350

RESUMO

Aim To report the first case of cardiac tamponade related to Infliximab induction therapy in an Ulcerative Colitis patient. Methods Review of published case reports. Results This complication was likely due to a type 3 hypersensitivity immune-complex reaction resulting in a reactive pericardial effusion Discussion Though rare, this case demonstrates how autoimmune reaction to anti-TNF𝛼 therapy can initially mimic infection, as our patient presented with tachycardia, hypotension, raised inflammatory and infective markers and fever.


Assuntos
Tamponamento Cardíaco/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Infliximab/efeitos adversos , Autoimunidade , Tamponamento Cardíaco/diagnóstico , Tamponamento Cardíaco/imunologia , Tamponamento Cardíaco/terapia , Colite Ulcerativa/imunologia , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/imunologia , Humanos , Infliximab/administração & dosagem , Infliximab/imunologia , Pessoa de Meia-Idade , Derrame Pericárdico/induzido quimicamente , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/imunologia , Derrame Pericárdico/terapia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologia
11.
Cochrane Database Syst Rev ; 5: CD001176, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31136680

RESUMO

BACKGROUND: Pouchitis occurs in approximately 50% of patients following ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis (UC). OBJECTIVES: The primary objective was to determine the efficacy and safety of medical therapies for prevention or treatment of acute or chronic pouchitis. SEARCH METHODS: We searched MEDLINE, Embase and CENTRAL from inception to 25 July 2018. We also searched references, trials registers, and conference proceedings. SELECTION CRITERIA: Randomized controlled trials of prevention or treatment of acute or chronic pouchitis in adults who underwent IPAA for UC were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently screened studies for eligibility, extracted data and assessed the risk of bias. The certainty of the evidence was evaluated using GRADE. The primary outcome was clinical improvement or remission in participants with acute or chronic pouchitis, or the proportion of participants with no episodes of pouchitis after IPAA. Adverse events (AEs) was a secondary outcome. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for each dichotomous outcome. MAIN RESULTS: Fifteen studies (547 participants) were included. Four studies assessed treatment of acute pouchitis. Five studies assessed treatment of chronic pouchitis. Six studies assessed prevention of pouchitis. Three studies were low risk of bias. Three studies were high risk of bias and the other studies were unclear.Acute pouchitis: All ciprofloxacin participants (7/7) achieved remission at two weeks compared to 33% (3/9) of metronidazole participants (RR 2.68, 95% CI 1.13 to 6.35, very low certainty evidence). No ciprofloxacin participants (0/7) had an AE compared to 33% (3/9) of metronidazole participants (RR 0.18, 95% CI 0.01 to 2.98; very low certainty evidence). AEs included vomiting, dysgeusia or transient peripheral neuropathy. Forty-three per cent (6/14) of metronidazole participants achieved remission at 6 weeks compared to 50% (6/12) of budesonide enema participants (RR 0.86, 95% CI 0.37 to 1.96, very low certainty evidence). Fifty per cent (7/14) of metronidazole participants improved clinically at 6 weeks compared to 58% (7/12) of budesonide enema participants (RR 0.86, 95% CI 0.42 to 1.74, very low certainty evidence). Fifty-seven per cent (8/14) of metronidazole participants had an AE compared to 25% (3/12) of budesonide enema participants (RR 2.29, 95% CI 0.78 to 6.73, very low certainty evidence). AEs included anorexia, nausea, headache, asthenia, metallic taste, vomiting, paraesthesia, and depression. Twenty-five per cent (2/8) of rifaximin participants achieved remission at 4 weeks compared to 0% (0/10) of placebo participants (RR 6.11, 95% CI 0.33 to 111.71, very low certainty evidence). Thirty-eight per cent (3/8) of rifaximin participants improved clinically at 4 weeks compared to 30% (3/10) of placebo participants (RR 1.25, 95% CI 0.34 to 4.60, very low certainty evidence). Seventy-five per cent (6/8) of rifaximin participants had an AE compared to 50% (5/10) of placebo participants (RR 1.50, 95% CI 0.72 to 3.14, very low certainty evidence). AEs included diarrhea, flatulence, nausea, proctalgia, vomiting, thirst, candida, upper respiratory tract infection, increased hepatic enzyme, and cluster headache. Ten per cent (1/10) of Lactobacillus GG participants improved clinically at 12 weeks compared to 0% (0/10) of placebo participants (RR 3.00, 95% CI 0.14 to 65.90, very low certainty evidence).Chronic pouchitis: Eighty-five per cent (34/40) of De Simone Formulation participants maintained remission at 9 to 12 months compared to 3% (1/36) of placebo participants (RR 20.24, 95% CI 4.28 to 95.81, 2 studies; low certainty evidence). Two per cent (1/40) of De Simone Formulation participants had an AE compared to 0% (0/36) of placebo participants (RR 2.43, 95% CI 0.11 to 55.89; low certainty evidence). AEs included abdominal cramps, vomiting and diarrhea. Fifty per cent (3/6) of adalimumab patients achieved clinical improvement at 4 weeks compared to 43% (3/7) of placebo participants (RR, 1.17, 95% CI 0.36 to 3.76, low certainty evidence). Sixty per cent (6/10) of glutamine participants maintained remission at 3 weeks compared to 33% (3/9) of butyrate participants (RR 1.80, 95% CI 0.63 to 5.16, very low certainty evidence). Forty-five per cent (9/20) of patients treated with bismuth carbomer foam enema improved clinically at 3 weeks compared to 45% (9/20) of placebo participants (RR 1.00, 95% CI 0.50 to 1.98, very low certainty evidence). Twenty-five per cent (5/20) of participants in the bismuth carbomer foam enema group had an AE compared to 35% (7/20) of placebo participants (RR 0.71, 95% CI 0.27 to 1.88, very low certainty evidence). Adverse events included diarrhea, worsening symptoms, cramping, sinusitis, and abdominal pain. PREVENTION: At 12 months, 90% (18/20) of De Simone Formulation participants had no episodes of acute pouchitis compared to 60% (12/20) of placebo participants (RR 1.50, 95% CI 1.02 to 2.21, low certainty evidence). Another study found 100% (16/16) of De Simone Formulation participants had no episodes of acute pouchitis at 12 months compared to 92% (11/12) of the no treatment control group (RR 1.10, 95% 0.89 to 1.36, very low certainty evidence). Eighty-six per cent (6/7) of Bifidobacterium longum participants had no episodes of acute pouchitis at 6 months compared to 60% (3/5) of placebo participants (RR 1.43, 95% CI 0.66 to 3.11, very low certainty evidence). Eleven per cent (1/9) of Clostridium butyricum MIYAIRI participants had no episodes of acute pouchitis at 24 months compared to 50% (4/8) of placebo participants (RR 0.22, 95% CI 0.03 to 1.60, very low certainty evidence). Forty-six per cent (43/94) of allopurinol participants had no episodes of pouchitis at 24 months compared to 43% (39/90) of placebo participants (RR 1.06, 95% CI 0.76 to 1.46; low certainty evidence). Eighty-one per cent (21/26) of tinidazole participants had no episodes of pouchitis over 12 months compared to 58% (7/12) of placebo participants (RR 1.38, 95% CI 0.83 to 2.31, very low certainty evidence). AUTHORS' CONCLUSIONS: The effects of antibiotics, probiotics and other interventions for treating and preventing pouchitis are uncertain. Well designed, adequately powered studies are needed to determine the optimal therapy for the treatment and prevention of pouchitis.


Assuntos
Anastomose Cirúrgica/efeitos adversos , Colite Ulcerativa/cirurgia , Pouchite/tratamento farmacológico , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Budesonida/efeitos adversos , Budesonida/uso terapêutico , Ciprofloxacino/efeitos adversos , Ciprofloxacino/uso terapêutico , Enema , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/uso terapêutico , Humanos , Metronidazol/efeitos adversos , Metronidazol/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/prevenção & controle , Pouchite/etiologia , Pouchite/prevenção & controle , Probióticos , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão
12.
Int J Mol Sci ; 20(10)2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126015

RESUMO

Inflammatory bowel disease (IBD) presents with disabling symptoms and may lead to insufficient growth and late pubertal development in cases of disease onset during childhood or adolescence. During the last decade, the role of anti-tumor necrosis factor (TNF) in the treatment of paediatric-onset IBD has gained more ground. The number of biologicals presently available for children and adolescents with IBD has increased, biosimilars have become available, and practices in adult gastroenterology with regards to anti-TNF have changed. The aim of this study is to review the current evidence on the indications, judicious use, effectiveness and safety of anti-TNF agents in paediatric IBD. A PubMed literature search was performed and included articles published after 2000 using the following terms: child or paediatric, Crohn, ulcerative colitis, inflammatory bowel disease, anti-TNF, TNF alpha inhibitor, infliximab, adalimumab, golimumab and biological. Anti-TNF agents, specifically infliximab and adalimumab, have proven to be effective in moderate and severe paediatric IBD. Therapeutic drug monitoring increases therapy effectiveness and safety. Clinical predictors for anti-TNF response are currently of limited value because of the variation in outcome definitions and follow-ups. Future research should comprise large cohorts and clinical trials comparing groups according to their risk profile in order to provide personalized therapeutic strategies.


Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Adalimumab/efeitos adversos , Adolescente , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Criança , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Humanos , Infliximab/efeitos adversos , Fator de Necrose Tumoral alfa/antagonistas & inibidores
13.
Expert Rev Gastroenterol Hepatol ; 13(6): 547-555, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31007098

RESUMO

INTRODUCTION: Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, are lifetime chronic and progressive disorders of poorly known etiology. Over the past few decades, new therapeutic approaches, including early and more aggressive intervention with immunomodulators and biological agents have offered the possibility of a favorable modification in the natural history of inflammatory bowel diseases. Area covered: Here, we review the literature about the effectiveness of early detection and intervention in adult inflammatory bowel diseases patients. Expert commentary: Detecting and managing early stages of inflammatory bowel diseases represents an effective strategy to avoid disease progression in selected patients. Primary care physicians may play a key role in attaining these outcomes by recognizing the signs and symptoms early and making timely referrals. Moreover, early therapeutic intervention with complete disease control may allow dose reduction or even treatment withdrawal in the maintenance phase, reducing side effects, costs, and also improving quality of life.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Diagnóstico Precoce , Fármacos Gastrointestinais/efeitos adversos , Humanos , Valor Preditivo dos Testes , Resultado do Tratamento
14.
Medicine (Baltimore) ; 98(15): e15189, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30985712

RESUMO

To determine the effect of prior corticosteroid treatment on the results of infliximab (IFX) therapy in patients with Crohn disease (CD).Patients with CD treated with at least 3 IFX infusions between March 2009 and April 2017 were divided into steroid group (n = 43) and nonsteroid group (n = 22) and analyzed retrospectively.The cumulative probabilities of clinical remission and response to IFX at weeks 14, 30, 54, and 78 were higher in the steroid group, though this difference was not statistical significant. At the mean interval of 11.7 months following the initiation of IFX treatment, the mucosal healing rate was significantly higher in the steroid group (71.0% vs 22.2%, P < .01). There was no statistical difference in the incidence of adverse reactions between the 2 groups.In CD, patients with prior corticosteroid treatment may increase the response rate to IFX therapy.


Assuntos
Corticosteroides/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Infliximab/uso terapêutico , Adolescente , Adulto , Feminino , Fármacos Gastrointestinais/efeitos adversos , Humanos , Infliximab/efeitos adversos , Masculino , Prednisona/uso terapêutico , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
15.
World J Gastroenterol ; 25(12): 1465-1477, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30948910

RESUMO

BACKGROUND: Anti-tumor necrosis factor α (TNFα) represents the best therapeutic option to induce mucosal healing and clinical remission in patients with moderate-severe ulcerative colitis. On the other side gut microbiota plays a crucial role in pathogenesis of ulcerative colitis but few information exists on how microbiota changes following anti-TNFα therapy and on microbiota role in mucosal healing. AIM: To elucidate whether gut microbiota and immune system changes appear following anti TNFα therapy during dextran sulfate sodium (DSS) colitis. METHODS: Eighty C57BL/6 mice were divided into four groups: "No DSS", "No DSS + anti-TNFα", "DSS" and "DSS + anti-TNFα". "DSS" and "DSS + anti-TNFα" were treated for 5 d with 3% DSS. At day 3, mice whithin "No DSS+anti-TNFα" and "DSS+anti-TNFα" group received 5 mg/kg of an anti-TNFα agent. Forty mice were sacrificed at day 5, forty at day 12, after one week of recovery post DSS. The severity of colitis was assessed by a clinical score (Disease Activity Index), colon length and histology. Bacteria such as Bacteroides, Clostridiaceae, Enterococcaceae and Fecalibacterium prausnitzii (F. prausnitzii) were evaluated by quantitative PCR. Type 1 helper T lymphocytes (Th1), type 17 helper T lymphocytes (Th17) and CD4+ regulatory T lymphocytes (Treg) distributions in the mesenteric lymph node (MLN) were studied by flow cytometry. RESULTS: Bacteria associated with a healthy state (i.e., such as Bacteroides, Clostridiaceae and F. prausnitzii) decreased during colitis and increased in course of anti-TNFα treatment. Conversely, microorganisms belonging to Enterococcaceae genera, which are linked to inflammatory processes, showed an opposite trend. Furthermore, in colitic mice treated with anti-TNFα microbial changes were associated with an initial increase (day 5 of the colitis) in Treg cells and a consequent decrease (day 12 post DSS) in Th1 and Th17 frequency cells. Healthy mice treated with anti-TNFα showed the same histological, microbial and immune features of untreated colitic mice. "No DSS + anti-TNFα" group showed a lymphomononuclear infiltrate both at 5th and 12th d at hematoxylin and eosin staining, an increase of in Th1 and Th17 frequency at day 12, an increase of Enterococcaceae at day 5, a decrease of Bacteroides and Clostridiaceae at day 12. CONCLUSION: Anti-TNFα treatment in experimental model of colitis improves disease activity but it is associated to an increase in Th17 pathway together with gut microbiota alteration.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Bactérias/efeitos dos fármacos , Bactérias/imunologia , Bactérias/isolamento & purificação , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/imunologia , Colo/efeitos dos fármacos , Colo/imunologia , Colo/microbiologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Microbioma Gastrointestinal/imunologia , Humanos , Infliximab/efeitos adversos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Índice de Gravidade de Doença , Células Th17/imunologia , Fator de Necrose Tumoral alfa/imunologia
16.
Expert Rev Gastroenterol Hepatol ; 13(6): 563-577, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31023087

RESUMO

INTRODUCTION: Managing fistulizing perianal disease is among the most challenging aspects of treating patients with Crohn's disease. Perianal fistulas are indicative of poor long-term prognosis. They are commonly associated with significant morbidities and can have detrimental effects on quality of life. While durable fistula closure is ideal, it is uncommon. In optimal circumstances, reported long-term fistula healing rates are only slightly higher than 50% and recurrence is common. Achieving these results requires a combined medical and surgical approach, highlighting the importance of a highly skilled and collaborative multidisciplinary team. In recent years, advances in imaging, biologic therapies and surgical techniques have lent to growing enthusiasm amongst treatment teams, however the most advantageous approach is yet to be determined. Areas covered: Here we review current management approaches, incorporating recent guidelines and novel therapies. Additionally, we discuss recently published and ongoing studies that will likely impact practice in the coming years. Expert opinion: Investing in concerted collaborative multi-institutional efforts will be necessary to better define optimal timing and dosing of medical therapy, as well as to identify ideal timing and approach of surgical interventions. Standardizing outcome measures can facilitate these efforts. Clearly, experienced multidisciplinary teams will be paramount in this process.


Assuntos
Doença de Crohn/terapia , Procedimentos Cirúrgicos do Sistema Digestório , Fármacos Gastrointestinais/uso terapêutico , Fístula Retal/terapia , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Quimioterapia Combinada , Fármacos Gastrointestinais/efeitos adversos , Humanos , Transplante de Células-Tronco Mesenquimais , Fístula Retal/diagnóstico , Fístula Retal/etiologia , Resultado do Tratamento
17.
Expert Opin Drug Saf ; 18(5): 357-367, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31026401

RESUMO

INTRODUCTION: Medications in treating Crohn's disease (CD) have evolved over the last two decades, particularly with the use of biologic agents. There are, however, concerns about the safety and adverse events associated with these medications. The authors review the safety profile of immunosuppressive medications used in Crohn's disease in adult patients. AREAS COVERED: The authors performed a literature search until October 2018 to examine safety data on thiopurines, methotrexate, anti-TNFα agents, vedolizumab and ustekinumab. The authors focused on 'trial' and 'real-world' data for the biologic agents. Safety in pregnancy and the elderly are also presented. EXPERT OPINION: Available data in CD suggest that immunosuppressive medications are relatively safe, although there are concerns about an elevated risk of serious infections, skin cancer and lymphoma particularly with thiopurines and anti-TNFα agents. Data on vedolizumab and ustekinumab suggest these newer biologic agents are well tolerated; however, longer term data in CD are required to identify risks with extended use. Apart from methotrexate, there appear to be no adverse congenital outcomes with exposure of drugs during pregnancy.


Assuntos
Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Imunossupressores/efeitos adversos , Adulto , Idoso , Fatores Biológicos/administração & dosagem , Fatores Biológicos/efeitos adversos , Doença de Crohn/fisiopatologia , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/farmacologia , Humanos , Imunossupressores/administração & dosagem , Gravidez , Fatores de Tempo , Fator de Necrose Tumoral alfa/antagonistas & inibidores
18.
Lancet ; 393(10182): 1699-1707, 2019 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-30929895

RESUMO

BACKGROUND: The infliximab biosimilar CT-P13 was approved for use in Crohn's disease after clinical comparison with originator infliximab in ankylosing spondylitis and rheumatoid arthritis; however, concerns about such indication extrapolation have been expressed. This study investigated whether CT-P13 is non-inferior to infliximab in patients with Crohn's disease who were naive to biological therapy. METHODS: In this randomised, multicentre, double-blind, phase 3 non-inferiority study, we enrolled patients with active Crohn's disease who had not responded to, or were intolerant to, non-biological treatments. Patients were randomly assigned (1:1:1:1) to receive CT-P13 then CT-P13, CT-P13 then infliximab, infliximab then infliximab, or infliximab then CT-P13, with switching occurring at week 30. Patients received 5 mg/kg CT-P13 or infliximab at weeks 0, 2, 6, and then every 8 weeks up to week 54. The primary endpoint was the proportion of patients with a decrease of 70 points or more in Crohn's Disease Activity Index (CDAI) from baseline to week 6. A non-inferiority margin of -20% was set (CT-P13 was non-inferior to infliximab if the lower limit of the two-sided 95% CI for the treatment difference was greater than -20). This trial is registered with ClinicalTrials.gov, number NCT02096861, and is completed. FINDINGS: Between Aug 20, 2014, and Feb 15, 2017, 308 patients were assessed for eligibility, and 220 patients were enrolled: 111 were randomly assigned to initiate CT-P13 (56 to the CT-P13-CT-P13 group and 55 to the CT-P13-infliximab group) and 109 to initiate infliximab (54 to the infliximab-infliximab group and 55 to the infliximab-CT-P13 group). CDAI-70 response rates at week 6 were similar for CT-P13 (77 [69·4%, 95% CI 59·9 to 77·8] of 111) and infliximab (81 [74·3%, 95% CI 65·1 to 82·2] of 109; difference -4·9% [95% CI -16·9 to 7·3]), thereby establishing non-inferiority. Over the total study period, 147 (67%) patients experienced at least one treatment-emergent adverse event (36 [64%] in the CT-P13-CT-P13 group, 34 [62%] in the CT-P13-infliximab group, 37 [69%] in the infliximab-infliximab group, and 40 [73%] in the infliximab-CT-P13 group). INTERPRETATION: This study showed non-inferiority of CT-P13 to infliximab in patients with active Crohn's disease. Biosimilar CT-P13 could be a new option for the treatment of active Crohn's disease. FUNDING: Celltrion, Pfizer.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Infliximab/uso terapêutico , Adulto , Anticorpos Monoclonais/efeitos adversos , Medicamentos Biossimilares/efeitos adversos , Método Duplo-Cego , Substituição de Medicamentos , Feminino , Fármacos Gastrointestinais/efeitos adversos , Humanos , Infliximab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
19.
Expert Rev Gastroenterol Hepatol ; 13(6): 557-561, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30947569

RESUMO

INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory condition that causes continuous mucosal inflammation of the colon. New biological drugs have been developed in order to avoid colectomy, but corticosteroids still play a crucial role in management of active UC. Areas covered: We reviewed the current literature about the importance of corticosteroid use in the treatment of ulcerative colitis. The evidence reviewed in this article is a summation of relevant scientific publications, expert opinion statements, and current practice guidelines. This review is a summary of expert opinion in the field without a formal systematic review of evidence. Expert opinion: Corticosteroids represent the mainstay of treatment in patients with severe UC and are very effective in inducing remission in mild to moderate flares not responding to combined oral and topical mesalazine. A valid alternative to systemic corticosteroids is represented by poorly absorbed steroids, such as Beclomethasone dipropionate and Budesonide MMX. In mild-moderate distal disease topical administration of corticosteroids (both systemic and BDP) is an effective alternative to topical mesalazine. However, corticosteroids do not represent a therapeutic option as a maintenance treatment since they are associated with multiple adverse effects.


Assuntos
Corticosteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Corticosteroides/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/imunologia , Fármacos Gastrointestinais/efeitos adversos , Humanos , Resultado do Tratamento
20.
J Dig Dis ; 20(5): 235-242, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30927309

RESUMO

OBJECTIVE: The study aimed to evaluate the long-term efficacy and safety of vedolizumab in a real-life cohort of patients with inflammatory bowel diseases enrolled at a tertiary referral center. METHODS: Data were retrospectively collected from August 2016 to November 2018. The primary outcomes were clinical response and remission at 14, 24, and 52 weeks, and steroid-free remission rate (SFRR) at 52 weeks. Endoscopic response and remission rates at 52 weeks were the secondary outcomes. RESULTS: Altogether 49 patients (22 with ulcerating colitis [UC] and 27 with Crohn's Disease [CD]) were enrolled. The clinical response rate gradually dropped from 85% and 50% in CD and UC, respectively, at week 14 to 59% and 25% at week 52, with significantly a higher response in CD at week 14. The endoscopic response at week 52 was 55% in CD and 25% in UC (P = 0.21). CD group had a higher SFRR than UC group (41% vs 20%) at 52 weeks, although the difference was not statistically significant. Similar clinical and endoscopic rates were observed in biologic-naive and -experienced patients. We reported no discontinuation due to adverse drug reactions, and only mild to moderate events. CONCLUSIONS: In our cohort the clinical response in the induction phase was similar to those of registered trials, despite surprising better results for CD. During the maintenance phase we observed an higher drop out than in the reported literatures. Of note, its good safety profile makes vedolizumab a reliable choice in patients with contraindications to anti-tumor necrosis factor agents.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Adolescente , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Esquema de Medicação , Quimioterapia Combinada , Feminino , Fármacos Gastrointestinais/efeitos adversos , Glucocorticoides/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Centros de Atenção Terciária , Resultado do Tratamento , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA