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1.
Artigo em Inglês | MEDLINE | ID: mdl-38750870

RESUMO

BACKGROUND & AIMS: Seventeen percent of patients with ulcerative colitis that undergo proctocolectomy with pouch surgery will develop chronic pouchitis. We evaluated the efficacy of ustekinumab for these patients. METHODS: We performed a prospective study of patients with chronic pouchitis receiving ustekinumab intravenously at baseline (∼6 mg/kg) and 90 mg ustekinumab subcutaneously every 8 weeks thereafter. The Modified Pouchitis Disease Activity Index (mPDAI) was assessed at baseline and weeks 16 and 48. The primary endpoint was the proportion of patients achieving steroid-free remission (mPDAI <5 and reduction by ≥2 points) at week 16. Secondary endpoints included the proportion of patients achieving remission at week 48, the proportion of patients achieving response (reduction of mPDAI by ≥2 points) at weeks 16 and 48, and change in mPDAI. RESULTS: We enrolled 22 patients (59% male; median age, 42.2 years). Remission was achieved in 27.3% at week 16 and 36.4% at week 48. Response was achieved in 54.5% both at weeks 16 and 48. The median mPDAI decreased from 8 (interquartile range [IQR], 7-10) to 7 (IQR, 4-9) at week 16 (P = .007) and 4 (IQR, 1.75-7.25) at week 48 (P < .001). The clinical mPDAI subscore decreased from 3.5 (IQR, 2-4) to 2 (IQR, 1-3) at week 16 (P = .009) and 1 (IQR, 0-2.25) at week 48 (P = .001). The endoscopic mPDAI subscore decreased from 5.5 (IQR, 4-6) to 4 (IQR, 3-6) at week 16 (P = .032) and 3 (IQR, 1.75-4.25) at week 48 (P = .001). CONCLUSION: Ustekinumab was efficacious in one-half of the patients suffering from chronic pouchitis. Ustekinumab should therefore be positioned in the treatment algorithm of chronic pouchitis. (ClinicalTrials.gov Number NCT04089345).

2.
Gastroenterology ; 163(5): 1294-1305.e3, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35940251

RESUMO

BACKGROUND & AIMS: Fatigue is highly prevalent among patients with inflammatory bowel disease (IBD), and only limited treatment options are available. Based on the hypothetical link between low serum tryptophan concentrations and fatigue, we determined the effect of 5-hydroxytryptophan supplementation on fatigue in patients with inactive IBD. METHODS: A multicenter randomized controlled trial was performed at 13 Belgian hospitals, including 166 patients with IBD in remission but experiencing fatigue, defined by a fatigue visual analog scale (fVAS) score of ≥5. Patients were treated in a crossover manner with 100 mg oral 5-hydroxytryptophan or placebo twice daily for 2 consecutive periods of 8 weeks. The primary end point was the proportion of patients reaching a ≥20% reduction in fVAS after 8 weeks of intervention. Secondary outcomes included changes in serum tryptophan metabolites, Functional Assessment of Chronic Illness Therapy Fatigue scale, and scores for depression, anxiety, and stress. The effect of the intervention on the outcomes was evaluated by linear mixed modeling. RESULTS: During 5-hydroxytryptophan treatment, a significant increase in serum 5-hydroxytryptophan (estimated mean difference, 52.66 ng/mL; 95% confidence interval [CI], 39.34-65.98 ng/mL; P < .001) and serotonin (3.0 ng/mL; 95 CI, 1.97-4.03 ng/mL; P < .001) levels was observed compared with placebo. The proportion of patients reaching ≥20% reduction in fVAS was similar in placebo- (37.6%) and 5-hydroxytryptophan (35.6%)-treated patients (P = .830). The fVAS reduction (-0.18; 95% CI, -0.81 to 0.46; P = .581) and Functional Assessment of Chronic Illness Therapy Fatigue scale increase (0.68; 95% CI, -2.37 to 3.73; P = .660) were both comparable between 5-hydroxytryptophan and placebo treatment as well as changes in depression, anxiety, and stress scores. CONCLUSIONS: Despite a significant increase in serum 5-hydroxytryptophan and serotonin levels, oral 5-hydroxytryptophan did not modulate IBD-related fatigue better than placebo. (Trial Registration: Belgian Federal Agency for Medication and Health Products, EudraCT number: 2017-005059-10 and ClinicalTrials.gov: NCT03574948, https://clinicaltrials.gov/ct2/show/NCT03574948.).


Assuntos
5-Hidroxitriptofano , Doenças Inflamatórias Intestinais , Humanos , 5-Hidroxitriptofano/uso terapêutico , Serotonina , Triptofano/uso terapêutico , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fadiga/tratamento farmacológico , Fadiga/etiologia , Doença Crônica
3.
Clin Gastroenterol Hepatol ; 19(6): 1180-1188.e4, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32777552

RESUMO

BACKGROUND/AIMS: Few data on the evolution of endoscopic findings are available in patients with acute severe ulcerative colitis (ASUC). The aim of this study was to describe this evolution in a prospective cohort. METHODS: Patients admitted for a steroid-refractory ASUC and included in a randomized trial comparing infliximab and cyclosporine were eligible if they achieved steroid-free clinical remission at day 98. Flexible sigmoidoscopies were performed at baseline, days 7, 42 and 98. Ulcerative colitis endoscopic index of severity (UCEIS) and its sub-scores - vascular pattern, bleeding and ulceration/erosion - were post-hoc calculated. Global endoscopic remission was defined by a UCEIS of 0, and partial endoscopic remission by any UCEIS sub-score of 0. RESULTS: Among the 55 patients analyzed (29 infliximab and 26 cyclosporine), 49 (83%) had UCEIS ≥6 at baseline at baseline. Partial endoscopic remission rates were higher for bleeding than for vascular pattern and for ulcerations/erosions at day 7 (20% vs. 4% and 5% (n = 55); p = .004 and p=.04), for bleeding and ulceration/erosion than for vascular pattern at day 42 [63% and 65% vs. 33% (n=54); p<.001 for both] and at day 98 [78% and 92% vs. 56% (n = 50); p = .007 and p < .001]. Global endoscopic remission rates at day 98 were higher in patients treated with infliximab than with cyclosporine [73% vs. 25% (n = 26 and 24); p < .001]. CONCLUSION: In steroid-refractory ASUC patients responding to a second-line medical therapy, endoscopic remission process started with bleeding remission and was not achieved in half the patients at day 98 for vascular pattern. Infliximab provided a higher endoscopic remission rate than cyclosporine at day 98.


Assuntos
Colite Ulcerativa , Colite Ulcerativa/tratamento farmacológico , Ciclosporina/uso terapêutico , Humanos , Infliximab/uso terapêutico , Estudos Prospectivos , Índice de Gravidade de Doença , Esteroides , Resultado do Tratamento
4.
Lancet ; 389(10080): 1699-1709, 2017 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-28411872

RESUMO

BACKGROUND: The interleukin-23 pathway is implicated genetically and biologically in the pathogenesis of Crohn's disease. We aimed to assess the efficacy and safety of risankizumab (BI 655066, Boehringer Ingelheim, Ingelheim, Germany), a humanised monoclonal antibody targeting the p19 subunit of interleukin-23, in patients with moderately-to-severely active Crohn's disease. METHODS: In this randomised, double-blind, placebo-controlled phase 2 study, we enrolled patients at 36 referral sites in North America, Europe, and southeast Asia. Eligible patients were aged 18-75 years, with a diagnosis of Crohn's disease for at least 3 months, assessed as moderate-to-severe Crohn's disease at screening, defined as a Crohn's Disease Activity Index (CDAI) of 220-450, with mucosal ulcers in the ileum or colon, or both, and a Crohn's Disease Endoscopic Index of Severity (CDEIS) of at least 7 (≥4 for patients with isolated ileitis) on ileocolonoscopy scored by a masked central reader. Patients were randomised 1:1:1 using an interactive response system to a double-blind investigational product, and stratified by previous exposure to TNF antagonists (yes vs no). Patients received intravenous 200 mg risankizumab, 600 mg risankizumab, or placebo, at weeks 0, 4, and 8. The primary outcome was clinical remission (CDAI <150) at week 12 (intention-to-treat population). Safety was assessed in patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02031276. FINDINGS: Between March, 2014, and September, 2015, 213 patients were screened, and 121 patients randomised. At baseline, 113 patients (93%) had been previously treated with at least one tumour necrosis factor (TNF) antagonist (which had failed in 96 [79%]). At week 12, 25 (31%) of 82 risankizumab patients (pooled 41 patients in 200 mg and 41 patients in 600 mg arms) had clinical remission versus six (15%) of 39 placebo patients (difference vs placebo 15·0%, 95% CI 0·1 to 30·1; p=0·0489). Ten (24%) of 41 patients who received 200 mg risankizumab had clinical remission (9·0%, -8·3 to 26·2; p=0·31) and 15 (37%) of 41 who received the 600 mg dose (20·9%, 2·6 to 39·2; p=0·0252). 95 (79%) patients had adverse events (32 in the placebo group, 32 randomised to 200 mg risankizumab, 31 randomised to 600 mg risankizumab); 18 had severe adverse events (nine, six, three); 12 discontinued (six, five, one); 24 had serious adverse events (12, nine, three). The most common adverse event was nausea and most common serious adverse event was worsening of underlying Crohn's disease. No deaths occurred. INTERPRETATION: In this short-term study, risankizumab was more effective than placebo for inducing clinical remission in patients with active Crohn's disease. Therefore, selective blockade of interleukin-23 via inhibition of p19 might be a viable therapeutic approach in Crohn's disease. FUNDING: Boehringer Ingelheim.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Subunidade p19 da Interleucina-23/antagonistas & inibidores , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
5.
Gastroenterology ; 150(2): 380-8.e4, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26632520

RESUMO

BACKGROUND & AIMS: Parenteral methotrexate is an effective treatment for patients with Crohn's disease, but has never been adequately evaluated in patients with ulcerative colitis (UC). We conducted a randomized controlled trial to determine its safety and efficacy in patients with steroid-dependent UC. METHODS: We performed a double-blind, placebo-controlled trial to evaluate the efficacy of parenteral methotrexate (25 mg/wk) in 111 patients with corticosteroid-dependent UC at 26 medical centers in Europe from 2007 through 2013. Patients were given prednisone (10 to 40 mg/d) when the study began and were randomly assigned to groups (1:1) given placebo or methotrexate (intramuscularly or subcutaneously, 25 mg weekly) for 24 weeks. The primary end point was steroid-free remission (defined as a Mayo score ≤2 with no item >1 and complete withdrawal of steroids) at week 16. Secondary endpoints included clinical remission (defined as a Mayo clinical subscore ≤2 with no item >1) and endoscopic healing without steroids at weeks 16 and/or 24, remission without steroids at week 24, and remission at both weeks 16 and 24. RESULTS: Steroid-free remission at week 16 was achieved by 19 of 60 patients given methotrexate (31.7%) and 10 of 51 patients given placebo (19.6%)--a difference of 12.1% (95% confidence interval [CI]: -4.0% to 28.1%; P = .15). The proportion of patients in steroid-free clinical remission at week 16 was 41.7% in the methotrexate group and 23.5% in the placebo group, for a difference of 18.1% (95% CI: 1.1% to 35.2%; P = .04). The proportions of patients with steroid-free endoscopic healing at week 16 were 35% in the methotrexate group and 25.5% in the placebo group--a difference of 9.5% (95% CI: -7.5% to 26.5%; P = .28). No differences were observed in other secondary end points. More patients receiving placebo discontinued the study because of adverse events (47.1%), mostly caused by UC, than patients receiving methotrexate (26.7%; P = .03). A higher proportion of patients in the methotrexate group had nausea and vomiting (21.7%) than in the placebo group (3.9%; P = .006). CONCLUSIONS: In a randomized controlled trial, parenteral methotrexate was not superior to placebo for induction of steroid-free remission in patients with UC. However, methotrexate induced clinical remission without steroids in a significantly larger percentage of patients, resulting in fewer withdrawals from therapy due to active UC. ClinicalTrials.gov ID NCT00498589.


Assuntos
Corticosteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colo/efeitos dos fármacos , Fármacos Gastrointestinais/uso terapêutico , Metotrexato/uso terapêutico , Corticosteroides/efeitos adversos , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Colite Ulcerativa/diagnóstico , Colo/patologia , Método Duplo-Cego , Quimioterapia Combinada , Europa (Continente) , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/efeitos adversos , Humanos , Injeções Intramusculares , Injeções Subcutâneas , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento , Cicatrização/efeitos dos fármacos
6.
J Pediatr Gastroenterol Nutr ; 63(2): 253-8, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26835906

RESUMO

OBJECTIVE: The Belgian registry for paediatric Crohn disease (BELCRO) cohort is a prospective, multicentre registry for newly diagnosed paediatric patients with Crohn disease (CD) (<18 years) recruited from 2008 to 2010 to identify predictive factors for disease activity and growth. METHODS: Data from the BELCRO database were evaluated at diagnosis, 24 and 36 months follow-up. RESULTS: At month 36 (M36), data were available on 84 of the 98 patients included at diagnosis. Disease activity evolved as follows: inactive 5% to 70%, mild 19% to 24%, and moderate to severe 76% to 6%. None of the variables such as age, sex, diagnostic delay, type of treatment, disease location, disease activity at diagnosis, and growth were associated with disease activity at M36. Paediatricians studied significantly less patients with active disease at M36 compared with adult physicians. Sixty percent of the patients had biologicals as part of their treatment at M36. Adult gastroenterologists initiated biologicals significantly earlier. They were the only factor determining biologicals' initiation, not disease location or disease severity at diagnosis. Median body mass index (BMI) z score evolved from -0.97 (range -5.5-2.1) to 0.11 (range -3.4-2) and median height z score from -0.15 (range -3.4-1.6) to 0.12 (range -2.3-2.3) at M36. None of the variables mentioned above influenced growth over time. CONCLUSIONS: Present treatment strategies lead to good disease control in the BELCRO cohort after 3 years. Logistic regression analysis did not show any influence of disease location or present treatment strategy on disease activity and growth, but patients under paediatric care had significantly less severe disease at M36.


Assuntos
Estatura , Índice de Massa Corporal , Doença de Crohn/diagnóstico , Progressão da Doença , Índice de Gravidade de Doença , Adolescente , Anti-Inflamatórios/uso terapêutico , Bélgica , Criança , Pré-Escolar , Colectomia , Terapia Combinada , Doença de Crohn/fisiopatologia , Doença de Crohn/terapia , Bases de Dados Factuais , Drenagem , Nutrição Enteral , Feminino , Seguimentos , Humanos , Ileostomia , Íleo/cirurgia , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Sistema de Registros , Adulto Jovem
7.
Clin Gastroenterol Hepatol ; 12(3): 423-31.e1, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24184736

RESUMO

BACKGROUND & AIMS: Monitoring plasma concentrations of anti-tumor necrosis factor agents could optimize treatment of patients with Crohn's Disease (CD). In a post hoc analysis of data from a clinical trial, we compared the relationship between plasma concentrations of certolizumab pegol (CZP) and endoscopic and clinical responses and remission with CZP therapy in patients with moderate to severe ileocolonic CD. METHODS: We analyzed data from the Endoscopic Mucosal Improvement in Patients with Active CD Treated with CZP trial, from 89 adult patients with active endoscopic CD (ulceration in ≥ 2 intestinal segments and CD Endoscopic Index of Severity [CDEIS] scores of ≥ 8 points). Patients received subcutaneous CZP (400 mg) at weeks 0, 2, and 4 and then every 4 weeks until week 52. Endoscopic evaluations were performed at weeks 0, 10, and 54. Blood samples were collected to measure CZP plasma concentrations at weeks 8 and 54. CZP quartiles at weeks 8 (n = 80) and 54 (n = 45) were correlated with endoscopic response (>5-point decrease in CDEIS from baseline) and remission (CDEIS, <6) at weeks 10 and 54, respectively. RESULTS: Higher concentrations of CZP at week 8 were associated with endoscopic response (P = .0016) and remission (P = .0302) at week 10 (n = 45). At week 54, the rates of endoscopic remission correlated with plasma concentrations of CZP (P = .0206). There was a significant inverse relationship between plasma concentrations of CZP and baseline levels of C-reactive protein and body weight (P = .0014 and P = .0373, respectively). CONCLUSIONS: Endoscopic response and remission are associated with higher plasma concentrations of CZP in patients with moderate to severe ileocolonic CD. These results support the need to consider the pharmacokinetics of anti-tumor necrosis factor agents and therapeutic drug monitoring to optimize treatment. Clinicaltrials.gov Number, NCT00297648.


Assuntos
Anticorpos Monoclonais Humanizados/sangue , Anticorpos Monoclonais Humanizados/uso terapêutico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/patologia , Fragmentos Fab das Imunoglobulinas/sangue , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Imunossupressores/sangue , Imunossupressores/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adolescente , Adulto , Anticorpos Monoclonais Humanizados/farmacocinética , Certolizumab Pegol , Colonoscopia , Feminino , Humanos , Imunossupressores/farmacocinética , Injeções Subcutâneas , Masculino , Plasma/química , Polietilenoglicóis/farmacocinética , Resultado do Tratamento , Adulto Jovem
8.
Gut ; 62(2): 201-8, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22525883

RESUMO

OBJECTIVE: To evaluate the efficacy of certolizumab pegol (CZP) in improving endoscopic lesions in patients with active ileocolonic Crohn's disease (CD). METHODS: This phase IIIB multicentre open-label clinical trial enrolled 89 adult patients with active endoscopic disease (ulceration in ≥2 intestinal segments with a Crohn's Disease Endoscopic Index of Severity (CDEIS) score ≥8 points). Patients received subcutaneous CZP 400 mg at weeks 0, 2 and 4 and every 4 weeks up to week 52. Endoscopic evaluations were performed at weeks 0, 10 and 54. The primary outcome was mean change in CDEIS score at week 10; secondary outcome measures included endoscopic response (decrease in CDEIS score >5 points), remission (CDEIS score <6), complete remission (CDEIS score <3) and mucosal healing (no ulcer) at weeks 10 and 54. RESULTS: In the intention-to-treat population (n=89) the mean±SD CDEIS score was 14.5±5.3 at baseline; the mean decrease in CDEIS score at week 10 was 5.7 (95% CI 4.6 to 6.8, p<0.0001). Rates of endoscopic response, endoscopic remission, complete endoscopic remission and mucosal healing at week 10 were 54%, 37%, 10% and 4%, respectively. At week 54 the corresponding rates were 49%, 27%, 14% and 8%, respectively. The safety profile was consistent with that of previous CZP trials. CONCLUSIONS: Following CZP treatment in patients with active CD, endoscopic lesions were improved as shown by the decrease in mean CDEIS score and by endoscopic response and remission rates. These benefits were achieved as early as week 10 and were generally maintained through week 54. CLINICAL TRIAL REGISTRATION NUMBER: NCT00297648.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Mucosa Intestinal/efeitos dos fármacos , Polietilenoglicóis/uso terapêutico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Certolizumab Pegol , Doença de Crohn/diagnóstico , Endoscopia Gastrointestinal , Feminino , Seguimentos , Humanos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Injeções Subcutâneas , Mucosa Intestinal/patologia , Masculino , Polietilenoglicóis/efeitos adversos , Indução de Remissão , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
9.
Lancet ; 380(9857): 1909-15, 2012 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-23063316

RESUMO

BACKGROUND: Ciclosporin and infliximab are potential rescue treatments to avoid colectomy in patients with acute severe ulcerative colitis refractory to intravenous corticosteroids. We compared the efficacy and safety of these drugs for this indication. METHODS: In this parallel, open-label, randomised controlled trial, patients were aged at least 18 years, had an acute severe flare of ulcerative colitis defined by a Lichtiger score greater than 10 points, and had been given an unsuccessful course of high-dose intravenous steroids. None of the patients had previously received ciclosporin or infliximab. Between June 1, 2007, and Aug 31, 2010, patients at 27 European centres were randomly assigned (via computer-derived permutation tables; 1:1) to receive either intravenous ciclosporin (2 mg/kg per day for 1 week, followed by oral drug until day 98) or infliximab (5 mg/kg on days 0, 14, and 42). In both groups, azathioprine was started at day 7 in patients with a clinical response. Neither patients nor investigators were masked to study treatment. The primary efficacy outcome was treatment failure defined by absence of a clinical response at day 7, a relapse between day 7 and day 98, absence of steroid-free remission at day 98, a severe adverse event leading to treatment interruption, colectomy, or death. Analysis was by intention to treat. This trial is registered with EudraCT (2006-005299-42) and ClinicalTrials.gov (NCT00542152). FINDINGS: 115 patients were randomly assigned; 58 patients were allocated to receive ciclosporin and 57 to receive infliximab. Treatment failure occurred in 35 (60%) patients given ciclosporin and 31 (54%) given infliximab (absolute risk difference 6%; 95% CI -7 to 19; p=0·52). Nine (16%) patients in the ciclosporin group and 14 (25%) in the infliximab group had severe adverse events. INTERPRETATION: Ciclosporin was not more effective than infliximab in patients with acute severe ulcerative colitis refractory to intravenous steroids. In clinical practice, treatment choice should be guided by physician and centre experience. FUNDING: Association François Aupetit, Société Nationale Française de Gastroentérologie, and the International Organization for the study of Inflammatory Bowel Disease.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Ciclosporina/uso terapêutico , Imunossupressores/uso terapêutico , Esteroides/administração & dosagem , Doença Aguda , Adulto , Resistência a Medicamentos , Feminino , Humanos , Infliximab , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Falha de Tratamento
10.
Eur J Clin Invest ; 43(3): 292-301, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23373823

RESUMO

BACKGROUND: Immunosuppressive drugs may prevent or partially reverse progression of renal AA-amyloidosis, a rare complication of Crohn's disease, often fatal due to renal failure. MATERIALS AND METHODS: The clinical, biological and pathological data of 16 patients treated since 1976 were reviewed. Serum amyloid A was determined in surviving patients. RESULTS: The median age of the 16 patients (13 men) was 23·5 years (range 16-69). At Crohn's disease onset, Montreal phenotypes were similar to reported data. Out of 15 patients with renal insufficiency, 8 developed a nephrotic syndrome and 7 a low grade proteinuria. The single patient without renal insufficiency had nephrotic syndrome. A significant correlation (P < 0·05) between the extension of renal amyloid A and sclerosis was found in 12 patients. One patient had a 10 year remission of nephrotic syndrome with immunosuppressive drugs. In 6 patients treated with anti-TNF-α (Tumor-Necrosis-Factor-α) agents, anaphylactic reaction (1/6), death from septic shock (1/6), 5-year remission (1/6) or reduction of nephrotic syndrome (1/6) and stabilization of renal insufficiency (2/6) were observed. Surgery was performed in 10 patients. Kidney transplantation was performed in 5 of the 8 patients dialysed for end-stage renal failure. Among 6/16 patients (37%) still alive, 3 belong to the 5 transplanted patients (survival: 3-20 years) and 3 to the anti-TNF-α drugs treated patients; all but one exhibited a low serum amyloid A level. CONCLUSIONS: Suppression of Crohn's disease inflammation potentially leads to the control of amyloid A production, assessed by a decrease of serum amyloid A. Kidney transplantation provides a long survival.


Assuntos
Amiloidose/prevenção & controle , Doença de Crohn/complicações , Nefropatias/prevenção & controle , Proteína Amiloide A Sérica/biossíntese , Adolescente , Adulto , Idade de Início , Idoso , Amiloidose/complicações , Amiloidose/mortalidade , Doença de Crohn/mortalidade , Doença de Crohn/prevenção & controle , Feminino , Humanos , Imunossupressores/uso terapêutico , Nefropatias/complicações , Nefropatias/mortalidade , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto Jovem
11.
Infect Prev Pract ; 5(1): 100267, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36601289

RESUMO

Background: Whether healthcare workers with inflammatory bowel disease (IBD) are at increased risk of Novel coronavirus disease (COVID-19) due to occupational exposure is unknown. Aim: To assess the risk of COVID-19 in healthcare workers with IBD. Methods: A case control study enrolled 326 healthcare workers with IBD from 17 GETAID centres and matched non-healthcare workers with IBD controls (1:1) for gender, age, disease subtype and year of diagnosis. The study period was year 2020 during the COVID-19 outbreak. Results: In total, 59 COVID-19 were recorded among cases (n = 32) and controls (n = 27), including 2 severe COVID-19 (requiring hospitalization, mechanic ventilation) but no death. No difference was observed between healthcare workers and controls regarding the overall incidence rates of COVID-19 4.9 ± 2.2 vs. 3.8 ± 1.9 per 100 patient-semesters, P = 0.34) and the overall incidence rates of severe COVID-19 (0.6 ± 7.8 vs. 0.3 ± 5.5 per 100 patient-semesters, P = 0.42). In multivariate analysis in the entire study population, COVID-19 was associated with patients with body mass index > 30 kg/m2 (HR = 2.48, 95%CI [1.13-5.44], P = 0.02). Conclusion: Healthcare workers with IBD do not have an increased risk of COVID-19 compared with other patients with IBD.

12.
Dig Liver Dis ; 55(10): 1338-1344, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37029063

RESUMO

BACKGROUND: Recent data regarding the impact of biologics and new surgical techniques on the indications and outcomes of colectomy for ulcerative colitis (UC) are limited. AIMS: The present study aimed at determining the trend of colectomy in UC by comparing colectomy indications and outcomes between 2000 and 2010 and 2011-2020. METHODS: This observational retrospective study was conducted in two tertiary hospitals, including consecutive patients who underwent colectomy between 2000 and 2020. All data concerning UC history, treatment and surgeries were collected. RESULTS: Among the 286 patients included, 87 underwent colectomy in 2001-2010 and 199 in 2011-2020. Patients' characteristics were similar between groups, except for prior biologic exposure (50.6 % vs. 74.9%; p<0.001). The indications of colectomy significantly decreased for refractory UC (50.6 % vs. 37.7%; p = 0.042), but were similar for acute severe UC (36.8 % vs. 42.2%; p = 0.390) and (pre)neoplastic lesions (12.6 % vs. 20.1%; p = 0.130). A widespread use of laparoscopy (47.7 % vs. 81.4%; p<0.001) was associated with fewer early complications (12.6 % vs. 5.5%; p = 0.038). CONCLUSION: Over the last two decades, the proportion of surgery for refractory UC significantly decreased compared to other surgical indications while surgical outcomes improved despite larger exposure to biologics.


Assuntos
Produtos Biológicos , Colite Ulcerativa , Laparoscopia , Humanos , Estudos Retrospectivos , Colite Ulcerativa/cirurgia , Colectomia/métodos , Produtos Biológicos/uso terapêutico
13.
Dig Liver Dis ; 55(12): 1632-1639, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37246095

RESUMO

BACKGROUND: In recent years, an increasing prevalence of obesity in inflammatory bowel disease (IBD) has been observed. However, only a few studies have focused on the impact of overweight and obesity on IBD-related disability. AIMS: To identify the factors associated with obese and overweight patients with IBD, including IBD-related disability. PATIENTS AND METHODS: In this cross-sectional study, we included 1704 consecutive patients with IBD in 42 centres affiliated with the Groupe d'Etude Therapeutique des Affections Inflammatoires du tube Digestif (GETAID) using a 4-page questionnaire. Factors associated with obesity and overweight were assessed using univariate and multivariate analyses (odds ratios (ORs) are provided with 95% confidence intervals). RESULTS: The prevalence rates of overweight and obesity were 24.1% and 12.2%, respectively. Multivariable analyses were stratified by age, sex, type of IBD, clinical remission and age at diagnosis of IBD. Overweight was significantly associated with male sex (OR = 0.52, 95% CI [0.39-0.68], p < 0.001), age (OR = 1.02, 95% CI [1.01-1.03], p < 0.001) and body image subscore (OR = 1.15, 95% CI [1.10-1.20], p < 0.001) (Table 2). Obesity was significantly associated with age (OR = 1.03, 95% CI [1.02-1.04], p < 0.001), joint pain subscore (OR = 1.08, 95% CI [1.02-1.14], p < 0.001) and body image subscore (OR = 1.25, 95% CI [1.19-1.32], p < 0.001) (Table 3). CONCLUSION: The increasing prevalence of overweight and obesity in patients with IBD is associated with age and poorer body image. A holistic approach to IBD patient care should be encouraged to improve IBD-related disability and to prevent rheumatological and cardiovascular complications.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Adulto , Humanos , Masculino , Estudos Transversais , Doença de Crohn/complicações , Doença de Crohn/epidemiologia , Sobrepeso/epidemiologia , Sobrepeso/complicações , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Obesidade/epidemiologia , Obesidade/complicações , Colite Ulcerativa/epidemiologia
14.
J Crohns Colitis ; 17(9): 1418-1425, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36988620

RESUMO

BACKGROUND: Fatigue is commonly reported by patients with inflammatory bowel disease [IBD], but the determinants of IBD-related fatigue have yet to be determined. AIMS: To identify the factors associated with fatigue in a large population of patients with IBD. PATIENTS AND METHODS: Fatigue and nine other IBD-related disability dimensions were assessed in a cohort of 1704 consecutive patients with IBD using the IBD-disk questionnaire in a cross-sectional survey of 42 French and Belgian centres. Fatigue and severe fatigue were defined as energy subscores >5 and >7, respectively. Determinants of fatigue were assessed using univariate and multivariate analyses (odds ratios [ORs] are provided with 95% confidence intervals). RESULTS: The prevalence rates of fatigue and severe fatigue were 54.1% and 37.1%, respectively. Both fatigue and severe fatigue were significantly higher in patients with active disease than in patients with inactive disease [64.9% vs 44.7% and 47.4% vs 28.6%, respectively; p < 0.001 for both comparisons]. In the multivariate analysis stratified by age, sex, type of IBD and IBD activity, fatigue was associated with age >40 years (OR = 0.71 [0.54-0.93]), female sex (OR = 1.48 [1.13-1.93]) and IBD-related sick leave (OR = 1.61 [1.19-2.16]), and joint pain (OR = 1.60 [1.17-2.18]), abdominal pain (OR = 1.78 [1.29-2.45]), regulating defecation (OR = 1.67 [1.20-2.32]), education and work (OR = 1.96 [1.40-2.75]), body image (OR = 1.38 [1.02-1.86]), sleep (OR = 3.60 [2.66-4.88]) and emotions (OR = 3.60 [2.66-4.88]) subscores >5. CONCLUSION: Determinants of fatigue are not restricted to IBD-related factors but also include social factors, sleep and emotional disturbances, thus supporting a holistic approach to IBD patient care.

15.
Gastrointest Endosc ; 73(3): 480-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21067735

RESUMO

BACKGROUND: Although colonoscopy is currently the optimal method for detecting colorectal polyps, some are missed. The Third Eye Retroscope provides an additional retrograde view that may detect polyps behind folds. OBJECTIVE: To determine whether the addition of the Third Eye Retroscope to colonoscopy improves the adenoma detection rate. DESIGN: Prospective, multicenter, randomized, controlled trial. SETTING: Nine European and U.S. centers. PATIENTS: Of 448 enrolled subjects, 395 had data for 2 procedures. INTERVENTIONS: Subjects underwent same-day tandem examinations with standard colonoscopy (SC) and Third Eye colonoscopy (TEC). Subjects were randomized to SC followed by TEC or TEC followed by SC. MAIN OUTCOME MEASUREMENTS: Detection rates for all polyps and adenomas with each method. RESULTS: In the per-protocol population, 173 subjects underwent SC and then TEC, and TEC yielded 78 additional polyps (48.8%), including 49 adenomas (45.8%). In 176 subjects undergoing TEC and then SC, SC yielded 31 additional polyps (19.0%), including 26 adenomas (22.6%). Net additional detection rates with TEC were 29.8% for polyps and 23.2% for adenomas. The relative risk of missing with SC compared with TEC was 2.56 for polyps (P < .001) and 1.92 for adenomas (P = .029). Mean withdrawal times for SC and TEC were 7.58 and 9.52 minutes, respectively (P < .001). The median difference in withdrawal times was 1 minute (P < .001). The mean total procedure times for SC and TEC were 16.97 and 20.87 minutes, respectively (P < .001). LIMITATIONS: Despite randomization and a large cohort, there was disparity in polyp prevalence between the 2 groups of subjects. CONCLUSION: The Third Eye Retroscope increases adenoma detection rate by visualizing areas behind folds. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01044732.).


Assuntos
Adenocarcinoma/diagnóstico , Adenoma/diagnóstico , Pólipos do Colo/diagnóstico , Colonoscopia/instrumentação , Neoplasias Colorretais/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Colonoscópios , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
16.
J Crohns Colitis ; 15(12): 2001-2010, 2021 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-34077509

RESUMO

BACKGROUND AND AIMS: Risankizumab, an interleukin-23 antibody, demonstrated efficacy and acceptable safety in a phase 2 study of patients with moderate-to-severe refractory Crohn's disease. This open-label extension investigated the long-term safety, pharmacokinetics, immunogenicity and efficacy of risankizumab in responders to risankizumab in the parent phase 2 study. METHODS: Enrolled patients had achieved clinical response [decrease in Crohn's Disease Activity Index from baseline ≥100] without clinical remission [Crohn's Disease Activity Index <150] at Week 26, or clinical response and/or remission at Week 52 in the parent phase 2 study and received open-label subcutaneous risankizumab 180 mg every 8 weeks. RESULTS: Sixty-five patients were enrolled, including four who had lost response in the parent study and were first reinduced with risankizumab 600 mg every 4 weeks [three infusions]. Patients received risankizumab for a median of 33 months [total: 167.0 patient-years]. The rate of serious adverse events was 24.6 events/100 patient-years; the majority were gastrointestinal in nature. Rates of serious infections, opportunistic infections and fungal infections were 4.2, 1.8, and 6.6 events/100 patient-years, respectively. No deaths, malignancies, adjudicated major adverse cardiovascular events, latent/active tuberculosis or herpes zoster were reported. Treatment-emergent anti-drug antibodies developed in eight patients [12.3%]; none were neutralizing. Efficacy outcomes were maintained during the study, including the proportions of patients [observed analysis] with clinical remission [>71%] and endoscopic remission [>42%]. CONCLUSIONS: Long-term maintenance treatment with subcutaneous risankizumab 180 mg every 8 weeks was well tolerated by patients with Crohn's disease, with no new safety signals. Clinical trial registration number: NCT02513459.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Infecções Oportunistas/etiologia , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/farmacocinética , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/farmacocinética , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
17.
Dig Liver Dis ; 53(4): 434-441, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33187920

RESUMO

BACKGROUND: Patients' experience with healthcare professionals could influence their clinical outcomes. AIMS: To assess inflammatory bowel disease (IBD) patients' experience with their disease, their treatment and their relationship with their physician. METHODS: A one-week cross-sectional study was conducted in 42 IBD centres. 2011 consecutive outpatients with IBD completed an anonymous self-report questionnaire assessing their experience with and knowledge of IBD. RESULTS: A quantitative assessment of the doctor-patient relationship revealed that patients' knowledge of IBD and IBD treatment ranged from 7.4 to 8.3 out of 10. In addition to IBD physicians, other sources of information about IBD and current treatment mainly included the internet (80% and 63%, respectively) and general practitioners (61% and 54%). Knowledge about education programmes (28%) was poor, resulting in a lack of willingness to further use these resources (25%). Concerns about IBD treatment were raised in 76% of patients, mostly related to the fear of adverse events (47%) and a lack of efficacy (33%). The need of alternative healthcare professionals was reported by 89% of the sample. CONCLUSION: In a large cohort of patients, we highlighted gaps in the management of patients with IBD regarding the need for higher-quality information and the implementation of alternative healthcare professionals.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Doenças Inflamatórias Intestinais/terapia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Relações Médico-Paciente , Médicos , Adulto , Bélgica , Estudos Transversais , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Autorrelato , Centros de Atenção Terciária
18.
J Crohns Colitis ; 15(5): 766-773, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33246337

RESUMO

BACKGROUND AND AIM: The inflammatory bowel disease [IBD]-disk is a 10-item self-questionnaire that is used to assess IBD-related disability. The aim of the present study was to evaluate this tool in the assessment of IBD daily-life burden. METHODS: A 1-week cross-sectional study was conducted in 42 centres affiliated in France and Belgium. Patients were asked to complete the IBD-disk [best score: 0, worst score: 100] and a visual analogue scale [VAS] of IBD daily-life burden [best score: 0, worst score: 10]. Analyses included internal consistency, correlation analysis, and diagnostic performance assessment. RESULTS: Among the 2011 IBD outpatients who responded to the survey [67.8% of the patients had Crohn's disease], 49.9% were in clinical remission. The IBD-disk completion rate was 73.8%. The final analysis was conducted in this population [n = 1455 patients]. The mean IBD-disk score and IBD daily-life burden VAS were 39.0 ± 23.2 and 5.2 ± 2.9, respectively. The IBD-disk score was well correlated with the IBD daily-life burden VAS [r = 0.67; p <0.001]. At an optimal IBD-disk cut-off of 40, the area under the receiver operating characteristic curve [AUROC] for high IBD daily-life burden [VAS >5] was 0.81 (95% confidence interval [CI]: 0.79-0.83; p <0.001). CONCLUSIONS: In a large cohort of patients, the IBD-disk score was well correlated with IBD daily-life burden, and it could be used in clinical practice.


Assuntos
Avaliação da Deficiência , Doenças Inflamatórias Intestinais/fisiopatologia , Adulto , Bélgica , Estudos Transversais , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade
19.
Eur J Clin Invest ; 40(11): 1037-47, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20629710

RESUMO

BACKGROUND: Thiopurines (TP) are widely used in the management of inflammatory bowel diseases. Side effects and inefficacy are a major concern as they lead to withdrawal of the drug. MATERIALS AND METHODS: Tools investigating TP metabolism are useful to avoid inadequate cessation of TP therapy. RESULTS: TP metabolism is complex and many enzymes are involved. Among them, Thiopurine methyl transferase is the only one routinely measured by pheno- or genotyping. A decreased TPMT activity results in a potential overdosing of TP drugs leading to myelotoxicity, whereas an ultra-high activity leads to TP ineffectiveness and overproduction of methylated compounds responsible for hepatotoxicity. TPMT determination prior to TP treatment results in an individual adapted dose. Xanthine oxidase/dehydrogenase (XOD), inosine triphosphate pyrophosphatase (ITPA) and glutathion-S-transferase (GST) are other promising enzyme targets that might help to explain TP efficacy or toxicity. ITPA and GST polymorphisms might potentially be related to some TP side effects, while a XOD inhibition by allopurinol could avoid TP-related hepatotoxicity. CONCLUSIONS: Utilization of thiopurine metabolites, 6-thioguanine nucleotides and 6-methylmercaptopurine, is discussed, specifically, in case of thiopurine failure and recommendations are given about their interpretation and potential dose optimization. These enzymes and metabolites tests are complementary to the regular monitoring of blood cells count and liver tests which remains mandatory.


Assuntos
Antimetabólitos/efeitos adversos , Fármacos Gastrointestinais/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Metiltransferases/metabolismo , Purinas/efeitos adversos , Tionucleotídeos/efeitos adversos , Antimetabólitos/farmacologia , Relação Dose-Resposta a Droga , Fármacos Gastrointestinais/farmacologia , Humanos , Doenças Inflamatórias Intestinais/genética , Metiltransferases/genética , Purinas/farmacologia , Tionucleotídeos/farmacologia
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