RESUMO
OBJECTIVES: Rescue therapy with either cyclosporine (CYS) or infliximab (IFX) is an effective option in patients with intravenous steroid-refractory attacks of ulcerative colitis (UC). In patients who fail, colectomy is usually recommended, but a second-line rescue therapy with IFX or CYS is an alternative. The aims of this study were to investigate the efficacy and tolerance of IFX and CYS as a second-line rescue therapy in steroid-refractory UC or indeterminate colitis (IC) unsuccessfully treated with CYS or IFX. METHODS: This was a retrospective survey of patients seen during the period 2000-2008 in the GETAID centers. Inclusion criteria included a delay of <1 month between CYS withdrawal (when used first) and IFX, or a delay of <2 months between IFX (when used first) and CYS, and a follow-up of at least 3 months after inclusion. Time-to-colectomy, clinical response, and occurrence of serious adverse events were analyzed. RESULTS: A total of 86 patients (median age 34 years; 49 males; 71 UC and 15 IC) were successively treated with CYS and IFX. The median (± s.e.) follow-up time was 22.6 (7.0) months. During the study period, 49 patients failed to respond to the second-line rescue therapy and underwent a colectomy. The probability of colectomy-free survival (± s.e.) was 61.3 ± 5.3% at 3 months and 41.3 ± 5.6 % at 12 months. A case of fatal pulmonary embolism occurred at 1 day after surgery in a 45-year-old man. Also, nine infectious complications were observed during the second-line rescue therapy. CONCLUSIONS: In patients with intravenous steroid-refractory UC and who fail to respond to CYS or IFX, a second-line rescue therapy may be effective in carefully selected patients, avoiding colectomy within 2 months in two-thirds of them. The risk/benefit ratio should still be considered individually.
Assuntos
Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Ciclosporina/administração & dosagem , Resistência a Medicamentos , Terapia de Salvação/métodos , Esteroides/administração & dosagem , Administração Oral , Adolescente , Adulto , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Criança , Colectomia , Colite Ulcerativa/cirurgia , Ciclosporina/efeitos adversos , Feminino , Seguimentos , Humanos , Infecções/induzido quimicamente , Infliximab , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/induzido quimicamente , Embolia Pulmonar/mortalidade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Anti-tumour necrosis factor (TNF) therapy may be associated with opportunistic infections (OIs). OBJECTIVE: To describe the spectrum of non-tuberculosis OIs associated with anti-TNF therapy and identify their risk factors. METHODS: A 3-year national French registry (RATIO) collected all cases of OI in patients receiving anti-TNF treatment for any indication in France. A case-control study was performed with three controls treated with anti-TNF agents per case, matched for gender and underlying inflammatory disease. RESULTS: 45 cases were collected of non-TB OIs in 43 patients receiving infliximab (n=29), adalimumab (n=10) or etanercept (n=4) for rheumatoid arthritis (n=26), spondyloarthritides (n=3), inflammatory colitis (n=8), psoriasis (n=1) or other conditions (n=5). One-third (33%) of OIs were bacterial (4 listeriosis, 4 nocardiosis, 4 atypical mycobacteriosis, 3 non-typhoid salmonellosis), 40% were viral (8 severe herpes zoster, 3 varicella, 3 extensive herpes simplex, 4 disseminated cytomegalovirus infections), 22% were fungal (5 pneumocystosis, 3 invasive aspergillosis, 2 cryptococcosis) and 4% were parasitic (2 leishmaniasis). Ten patients (23%) required admission to the intensive care unit, and four patients (9%) died. Risk factors for OIs were treatment with infliximab (OR=17.6 (95% CI 4.3 - 72.9); p<0.0001)or adalimumab (OR=10.0 (2.3 to 44.4); p=0.002) versus etanercept, and oral steroid use >10 mg/day or intravenous boluses during the previous year (OR=6.3 (2.0 to 20.0); p=0.002). CONCLUSION: Various and severe OIs, especially those with intracellular micro-organisms, may develop in patients receiving anti-TNF treatment. Monoclonal anti-TNF antibody rather than soluble TNF receptor therapy and steroid use >10 mg/day are independently associated with OI.
Assuntos
Anti-Inflamatórios/efeitos adversos , Antirreumáticos/efeitos adversos , Fatores Imunológicos/efeitos adversos , Infecções Oportunistas/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Métodos Epidemiológicos , Etanercepte , Feminino , França/epidemiologia , Humanos , Imunoglobulina G/efeitos adversos , Infliximab , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/epidemiologia , Receptores do Fator de Necrose TumoralRESUMO
BACKGROUND: The function of eosinophils has been attributed to host defense, immunomodulation, and fibrosis. Although eosinophils are found among infiltrating cells in a broad spectrum of skin diseases, their pathogenic role remains uncertain. This study aimed to analyze the cytokine expression by eosinophils in different skin diseases. METHODS: Skin specimens from different skin diseases [allergic/reactive, infectious, autoimmune, and tumors/lymphomas (LY)] were stained by antibodies directed to eosinophil cationic protein, cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-5, IL-6, IL-10, IL-11, IL-13, IL-17, IL-25, IL-33, interferon-γ, transforming growth factor (TGF)-ß, and thymic stromal lymphopoietin], eotaxins (CCL11, CCL24, and CCL26), metalloproteinase (MMP)-9 as well as extracellular matrix proteins (tenascin-C and procollagen-3) and then analyzed by laser scanning microscopy. RESULTS: The number of eosinophils varied considerably in and between disease groups and did not correlate with the numbers of accompanying inflammatory cells. The expression of IL-5, IL-6, IL-11, TGF-ß, CCL24, and MMP-9 by eosinophils significantly differed between disease groups. Eosinophils in tumors/LY predominantly expressed IL-6, TGF-ß, and CCL24, but not IL-11. On the other hand, in autoimmune diseases, eosinophils largely contributed to MMP-9 production. IL-5-generating eosinophils were particularly obvious in allergic and infectious diseases. CONCLUSION: In skin diseases, eosinophil expresses a broad spectrum of cytokines. The different cytokine expression patterns suggest distinct functional roles of eosinophils in these diseases that might be related to host defense, immunomodulation, fibrosis, and/or tumor development.
Assuntos
Citocinas/metabolismo , Eosinófilos/imunologia , Dermatopatias/classificação , Dermatopatias/imunologia , Doenças Autoimunes/imunologia , Biópsia , Eosinófilos/metabolismo , Fibrose/imunologia , Humanos , Hipersensibilidade/imunologia , Infecções/etiologia , Infecções/imunologia , Neoplasias/imunologia , Pele/imunologiaRESUMO
OBJECTIVE: To describe cases of lymphoma associated with anti-TNF therapy, identify risk factors, estimate the incidence and compare the risks for different anti-TNF agents. METHODS: A national prospective registry was designed (Research Axed on Tolerance of bIOtherapies; RATIO) to collect all cases of lymphoma in French patients receiving anti-TNF therapy from 2004 to 2006, whatever the indication. A case-control analysis was conducted including two controls treated with anti-TNF per case and an incidence study of lymphoma with the French population was used as the reference. RESULTS: 38 cases of lymphoma, 31 non-Hodgkin's lymphoma (NHL) (26 B cell and five T cell), five Hodgkin's lymphoma (HL) and two Hodgkin's-like lymphoma were collected. Epstein-Barr virus was detected in both of two Hodgkin's-like lymphoma, three of five HL and one NHL. Patients receiving adalimumab or infliximab had a higher risk than those treated with etanercept: standardised incidence ratio (SIR) 4.1 (2.3-7.1) and 3.6 (2.3-5.6) versus 0.9 (0.4-1.8). The exposure to adalimumab or infliximab versus etanercept was an independent risk factor for lymphoma in the case-control study: odds ratio 4.7 (1.3-17.7) and 4.1 (1.4-12.5), respectively. The sex and age-adjusted incidence rate of lymphoma was 42.1 per 100 000 patient-years. The SIR was 2.4 (95% CI 1.7 to 3.2). CONCLUSION: The two to threefold increased risk of lymphoma in patients receiving anti-TNF therapy is similar to that expected for such patients with severe inflammatory diseases. Some lymphomas associated with immunosuppression may occur, and the risk of lymphoma is higher with monoclonal-antibody therapy than with soluble-receptor therapy.
Assuntos
Antirreumáticos/efeitos adversos , Imunossupressores/efeitos adversos , Linfoma/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Idoso , Antirreumáticos/uso terapêutico , Artrite/tratamento farmacológico , Métodos Epidemiológicos , Feminino , França/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Linfoma/epidemiologia , Linfoma/imunologia , Masculino , Pessoa de Meia-Idade , Sistema de RegistrosRESUMO
OBJECTIVES: Inflammatory bowel disease (IBD), e.g., Crohn's disease (CD) and ulcerative colitis (UC), is a complex genetic disorder. Tumor necrosis factor (ligand) superfamily, member 15 (TNFSF15) has been previously identified as a susceptibility gene for CD in Japanese and UK cohorts. This replication study was designed in order to confirm and further validate the role of TNFSF15 in IBD. METHODS: A total of 666 IBD families (corresponding to 2,982 relatives) with European ancestry were genotyped for the rs6478108 and rs7869487 polymorphisms, which define the main TNFSF15 haplotypes previously associated with CD. An association between the main haplotypes and CD, UC and IBD was tested using the Genehunter TDT and Unphased statistics. Caspase recruitment domain 15 (CARD15)/TNFSF15 interaction and genotype/phenotype correlations were also studied. RESULTS: The previously reported "high-risk" haplotype (A) was associated with IBD (P=0.001) (OR=1.25 (1.05-1.50)) and CD (P=0.02) (OR=1.31 (1.03-1.67)) whereas the "protective" (B) haplotype was significantly less transmitted to IBD and CD patients. No interaction between CARD15 and TNFSF15 was detected. We also failed to define a clinical subgroup of CD patients specifically associated with TNFSF15 haplotype A. CONCLUSIONS: This study confirms that TNFSF15 or a closely linked gene is involved in the genetic predisposition to CD.
Assuntos
Colite Ulcerativa/genética , Doença de Crohn/genética , Polimorfismo de Nucleotídeo Único/genética , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , População Branca/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Europa (Continente) , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Proteína Adaptadora de Sinalização NOD2/genética , Adulto JovemRESUMO
STUDY: A comparative study which compared PPD skin testing inserted according to the French Society of Pneumology's recommendations and interferon gamma release assay (IGRA) (QuantiFERON((R)) TB Gold In-tube, QF-TB-IT, Cellestis, Carnegie, Australia) was performed during a tuberculosis contact investigation in our hospital. PATIENTS: Nineteen French health-care workers (HCWs) volunteered to participate. All of the HCW enrolled were BCG vaccinated and had a normal chest X-ray at entry. RESULTS: Among the HCW, 68.4% were TST positive. By comparison, only 31.6% had a positive QF-TB-IT result. We took advantage of the negative tube and the corresponding plasma for antibody detection by ELISA. None were ELISA positive. Fourteen HCWs were followed up. None of the HCWs accepted a course of antiTB chemoprophylaxis. Despite the difficulty in establishing a trend in kinetics, we saw the complexity of interpretation of a dynamic T-cell response after contact with an index case. CONCLUSION: This initial and first French picture provides us with the observation that only 44% of TST-positive HCW were IGRA positive, and the IGRA test allowed the detection of LTBI in two TST negative HCWs.
Assuntos
Anticorpos/sangue , Busca de Comunicante/métodos , Interferon gama/imunologia , Mycobacterium tuberculosis/imunologia , Enfermeiras e Enfermeiros , Tuberculose/imunologia , Adulto , Formação de Anticorpos , Vacina BCG/administração & dosagem , Ensaio de Imunoadsorção Enzimática , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia Torácica , Fatores de Risco , Sensibilidade e Especificidade , Teste Tuberculínico , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Adulto JovemRESUMO
This study investigated the long-term outcome of patients with tuberculosis (TB) as a complication of tumour necrosis factor (TNF)-alpha blocker therapy. All TB cases (n = 21) complicating TNF-alpha blocker therapy from French university hospitals were collated between January 2000 and September 2002. Outcome was assessed via a postal questionnaire during September 2005. The mortality rate after 4 years was 4.8%, and one patient had relapsed and six (29%) patients had recommenced TNF-alpha antagonist treatment, after appropriate anti-TB therapy, without reactivation. These data support the concept that TNF-alpha antagonists can be restarted in TB patients provided that adequate anti-TB treatment has been completed.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Tuberculose/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Antituberculosos/uso terapêutico , Artrite Reumatoide/complicações , Feminino , Seguimentos , França/epidemiologia , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Infliximab , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Resultado do Tratamento , Tuberculose/tratamento farmacológico , Tuberculose/mortalidadeRESUMO
Colonic lipoma is a rare benign tumor infrequently met in clinical practice. We report a case of symptomatic lipoma of the ascending colon in a 61-year-old woman. Diagnosis was suspected on CT scan. Colotomy with lipectomy was performed. The diagnosis was confirmed by histological examination. Reviewing the literature and combining with our experience, we discuss the clinical features, diagnosis and treatment of this uncommon disease.
Assuntos
Neoplasias do Colo , Lipoma , Neoplasias do Colo/cirurgia , Feminino , Humanos , Lipoma/diagnóstico , Pessoa de Meia-IdadeRESUMO
Acute pancreatitis is not infrequent after allogenic marrow transplantation. Several causes can predispose to pancreatitis, including Graft-Versus-Host Disease (GVHD), a condition which is probably underestimated. In the literature, few description of pancreatic GVHD can be found. Pancreatic GVHD diagnosis can be difficult if pancreatic involvement occurs without other typical manifestations of GVHD. We report the case of a woman, 54 years old, suffering from prolonged, painful pancreatitis two months after allogenic bone marrow transplantation for acute myeloid leucemia. Pancreatic GVHD diagnosis was performed after five weeks on duodenal biopsies despite the absence of diarrheoa. The patient dramatically improved within few days on corticosteroids.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Pancreatite/etiologia , Doença Aguda , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de TempoRESUMO
BACKGROUND: Patients treated with tumor necrosis factor-alpha (TNF-alpha) antagonists have an increased risk of infection, but infection due to Legionella pneumophila has rarely been described in patients receiving such therapy. METHODS: A registry involving 486 clinical departments in France was designed by a multidisciplinary group (Recherche Axée sur la Tolérance des Biothérapies [RATIO]) to collect data on opportunistic and severe infections occurring in patients treated with TNF-alpha antagonists. All cases are reported to RATIO in accordance with national health authorities and validated by infectious disease experts. The legionellosis rate among patients treated with TNF-alpha antagonists was compared with the rate in France overall. RESULTS: We report a 1-year consecutive series of 10 cases of L. pneumophila pneumonia in France in 2004, including 6 cases treated with adalimumab, 2 treated with etanercept, and 2 treated with infliximab. The median patient age was 51 years (range, 40-69 years). Eight patients were treated for rheumatoid arthritis, 1 was treated for cutaneous psoriasis, and 1 was treated for pyoderma gangrenosum. The median duration of TNF-alpha antagonist treatment at onset of infection was 38.5 weeks (range, 3-73 weeks). Eight patients were receiving concomitant treatment with corticosteroids, and 6 were receiving treatment with methotrexate. The relative risk of legionellosis when receiving treatment with a TNF-alpha antagonist, compared with the relative risk in France overall, was estimated to be between 16.5 and 21.0. We also report a second episode of confirmed legionellosis following the reintroduction of infliximab therapy. CONCLUSIONS: L. pneumophila pneumonia is a potentially severe but curable infection that might complicate anti-TNF-alpha therapy. In patients receiving anti-TNF-alpha who develop pneumonia, legionellosis should be systematically investigated, and first-line antibiotic therapy should be efficient against L. pneumophila.
Assuntos
Legionella pneumophila , Doença dos Legionários/tratamento farmacológico , Pneumonia/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Adulto , Idoso , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Doenças Transmissíveis Emergentes/tratamento farmacológico , Etanercepte , Feminino , Humanos , Imunoglobulina G/uso terapêutico , Infliximab , Masculino , Pessoa de Meia-Idade , Receptores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
The decision regarding prophylactic treatment after surgery in Crohn's disease (CD) requires a good estimation of the risk of recurrence. It is also important to consider the consequences of recurrence for the patient, and the risks and benefits of treatment, bearing in mind that it will be given over a long period. Several drugs have been tried to decrease the risk of recurrence. Corticosteroids and budesonide have proved to be ineffective. Mesalazine has significant efficacy in some, but not all trials, and a meta-analysis has established that it decreases the absolute risk by 10-15% after 1-2 years. Mercaptopurine seemed to be effective in a recent study. Metronidazole and ornidazole have significant efficacy, but cannot be tolerated for long periods. Probiotics represent a new approach, but evidence for their efficacy in CD is still lacking. In the past, the strategy was to give no treatment until clinical recurrence. Another approach is to give no treatment, and then to treat the patient according to severity of endoscopic recurrence. Alternative strategies include treating all patients with mesalazine until either severe endoscopic or clinical recurrence occurs, and then to use azathioprine/mercaptopurine, or to give azathioprine/mercaptopurine immediately, especially in high-risk patients.
Assuntos
Doença de Crohn/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Prevenção Secundária , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Doença de Crohn/tratamento farmacológico , Humanos , Probióticos/uso terapêutico , Fatores de RiscoRESUMO
Lactulose (10-20 g day(-1)) is used to treat constipation. At this therapeutic dose, its effects on colonic motility remain unknown. Twenty-two healthy subjects swallowed a probe with an infusion catheter, six perfused catheters and a balloon connected to a barostat. Colonic phasic and tonic motor activity was recorded in fasting state. In group 1, four volunteers ingested 15 g lactulose and motility was recorded for 5 h after entry of lactulose into the caecum; in group 2, motility was recorded during (3 h) and 2 h after intracolonic infusion of isoosmotic and isovolumetric solutions containing sodium chloride alone (n = 9) or with 15 g lactulose (n = 9). In a last group of volunteers, isotopic colonic transit after ingestion of lactulose (10 g,n = 9) was assessed and compared with a control group (n = 17). Ingestion or intracolonic infusion of 15 g lactulose significantly decreased barostat bag volume (maximal decrease: 45 +/- 12% and 35 +/- 9% of basal value respectively). Phasic contractions remained unchanged. Tonic and phasic motility was unchanged by the isotonic and isovolumetric infusion of saline. Ingestion of lactulose significantly accelerated isotopic colonic transit time compared with the control group. We conclude that in healthy humans, 10-15 g ingestion or intracaecal infusion of lactulose produces a prolonged tonic contraction that may be involved in the laxative effect of lactulose.
Assuntos
Catárticos/farmacologia , Colo/efeitos dos fármacos , Lactulose/farmacologia , Administração Oral , Adulto , Testes Respiratórios , Catárticos/administração & dosagem , Catárticos/metabolismo , Colo/diagnóstico por imagem , Enema , Feminino , Fermentação , Motilidade Gastrointestinal/efeitos dos fármacos , Humanos , Hidrogênio/metabolismo , Radioisótopos de Índio , Lactulose/administração & dosagem , Lactulose/metabolismo , Masculino , Metano/metabolismo , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Concentração Osmolar , CintilografiaRESUMO
BACKGROUND: The impact of pregnancy on Crohn's disease activity has been poorly investigated. AIM: To determine the effect of pregnancy on Crohn's disease activity from the retrospective analysis of a cohort of women who had a regular clinical follow-up. METHODS: Seventy pregnancies occurring in 61 women were studied. The Harvey-Bradshaw index was determined during the four quarters preceding each pregnancy, the three quarters of pregnancy and the four quarters following delivery. RESULTS: The mean Harvey-Bradshaw index during pregnancy [0.68 (0.18), mean (S.E.M.)] was significantly lower than that of the year preceding pregnancy [0.98 (0.16), P = 0.03] and that of the year following delivery [1.10 (0.17), P = 0.04]. In non-smoking women (48 pregnancies), there was no significant change of Harvey-Bradshaw index between these intervals. Whereas in those who smoked (22 pregnancies), most of whom reduced tobacco consumption during pregnancy, the mean Harvey-Bradshaw index during pregnancy was significantly reduced compared with that of the year following delivery [0.58 (0.20) vs. 1.60 (0.33), P = 0.01]. The use of drugs was significantly lower during pregnancy. CONCLUSIONS: Crohn's disease activity is mildly but significantly lower during pregnancy. The reduction of tobacco consumption during pregnancy in smoking women may play an important role in this improvement.
Assuntos
Doença de Crohn/etiologia , Complicações na Gravidez/etiologia , Adulto , Estudos de Coortes , Doença de Crohn/tratamento farmacológico , Doença de Crohn/cirurgia , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/cirurgia , Resultado da Gravidez , Estudos RetrospectivosRESUMO
The effect of the energy density of a meal on gastric emptying and satiety was assessed in nine volunteers. They ingested, in randomized order, a diluted (2671 kJ/L, 950 mL) and a concentrated (7452 kJ/L, 350 mL) test meal of 2500 kJ each (80% as solids). Half-emptying times of solids and liquids were not significantly different for the diluted and concentrated meal (solids: 145 +/- 18 and 156 +/- 16 min, respectively; liquids: 76 +/- 10 and 84 +/- 10 min, respectively), and consequently, pyloric outputs of energy were identical. Neither the intensity and duration of satiety, nor the amount of energy ingested, ad libitum, 6 h after the test meal, were significantly affected by energy density of the food ingested. Both the intensity and duration of satiety correlated significantly with the gastric emptying time for solids (r = 0.60 and 0.67, respectively, P < 0.01). These results show that satiety depends on gastric emptying of energy and is not affected by the energy density of food intake.
Assuntos
Ingestão de Energia/fisiologia , Alimentos , Esvaziamento Gástrico/fisiologia , Saciação/fisiologia , Adolescente , Adulto , Análise de Variância , Feminino , Humanos , Masculino , CintilografiaRESUMO
BACKGROUND: Little information is available about the safety of high doses of mesalazine during pregnancy. AIM: To study the fate of pregnancy and foetal outcome in women taking 1-4 g/day of mesalazine microgranules for inflammatory bowel disease. PATIENTS AND METHODS: Case reports were collected from the Pharmacovigilance Department of Ferring SA, France, from a survey conducted in three gastroenterology units, and from a teratology information service. The evolution of pregnancy and foetal outcome were assessed by questionnaire. RESULTS: The study covered a total of 123 pregnancies (126 foetuses). Ninety-six women took mesalazine during the first trimester, 85 during the second and 83 during the third. The mean daily dose was 2.1+/-0.8 g; 86 women received <3 g/day (low-dose group), 37 women received > or =3 g/day (high-dose group). The following abnormalities were observed in the low-dose and high-dose groups, respectively: ectopic pregnancy (1/0), spontaneous abortions (1/1), foetal death (0/1), premature deliveries (3/5, P < 0.05), congenital malformations (3/1) and one case of lethal oxalosis. Abnormalities were not considered to be related to mesalazine. CONCLUSIONS: The use of oral mesalazine microgranules during pregnancy is safe at doses < or =2 g/day, and probably also at a dose of 3 g/day.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mesalamina/administração & dosagem , Complicações na Gravidez/tratamento farmacológico , Resultado da Gravidez , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Distribuição de Qui-Quadrado , Esquema de Medicação , Feminino , Humanos , Mesalamina/efeitos adversos , Gravidez , Estudos Prospectivos , Estudos Retrospectivos , Estatísticas não Paramétricas , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Infliximab, a chimeric monoclonal antibody to tumour necrosis factor-alpha, is a new potent therapy for active Crohn's disease, but induces short-lived improvements. AIM: To evaluate the efficacy of thalidomide, a drug with anti-tumour necrosis factor-alpha activity, for the maintenance of infliximab-induced response in refractory Crohn's disease. METHODS: Fifteen patients with severe, refractory disease (10 females, five males; mean age, 40 years; eight with luminal disease, two with fistulizing disease and five with both luminal and fistulizing disease) were started on thalidomide (100 mg daily), 29 +/- 10 days after they had responded to infliximab (5 mg/kg infusions). RESULTS: The median follow-up period was 238 days (range, 10-458 days) from the initiation of thalidomide and 265 days (range, 10-537 days) from the last infliximab infusion. The median Crohn's disease activity indices were 322 (range, 170-525), 119 (range, 24-503) and 35 (range, -60-360) before infliximab, at the initiation of thalidomide and at the end of follow-up, respectively. Remission rates on thalidomide were 92%, 83% and 83% at 3, 6 and 12 months, respectively, after the last infliximab infusion (Kaplan-Meier). Four patients (two in remission) stopped thalidomide for suspected adverse effects. Side-effects (drowsiness, rash and peripheral neuropathy) were mild and mostly transient. CONCLUSIONS: Thalidomide appears to be an effective and relatively safe drug to maintain response to infliximab in chronically active and fistulizing refractory Crohn's disease.
Assuntos
Anticorpos Monoclonais/farmacologia , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Fístula/tratamento farmacológico , Fístula/etiologia , Fármacos Gastrointestinais/farmacologia , Imunossupressores/farmacologia , Talidomida/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Doença Crônica , Resistência a Medicamentos , Feminino , Fármacos Gastrointestinais/administração & dosagem , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Infliximab , Masculino , Índice de Gravidade de Doença , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Intensive intravenous treatment remains the first line therapy of severe, uncomplicated attacks of ulcerative colitis. AIM: To predict the failure of intensive intravenous treatment by combining clinical and laboratory parameters with endoscopy findings. METHODS: Retrospective study conducted in a tertiary care referral centre. Failure of intensive intravenous treatment was defined as colectomy before day 30, intravenous cyclosporin, or death. Predictive factors of outcome were assessed using univariate and multivariate prognostic analysis. RESULTS: Between January 1990 and May 1997, 85 consecutive patients were treated with intensive intravenous treatment for non-response to oral corticosteroids (n=59) and/or severe attack of ulcerative colitis (n=26). There were 41 successes and 44 failures (including 1 death, 13 cyclosporin and 30 colectomies before day 30). Multivariate prognostic analysis found that the presence of Truelove and Witts' criteria (P=0.018), an attack that had lasted more than 6 weeks (P=0.001), and severe endoscopic lesions (P=0.007) were associated with an increased risk of failure. Patients with severe endoscopic lesions and Truelove and Witts' criteria, or an attack of more than 6 weeks had a failure rate of 85-86%. CONCLUSION: Clinical, laboratory and endoscopic findings can predict the risk of failure of intensive intravenous treatment. A prospective study is required to confirm these results.
Assuntos
Colite Ulcerativa/terapia , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/mortalidade , Colonoscopia , Cuidados Críticos , Feminino , Seguimentos , Humanos , Injeções Intravenosas , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Esteroides , Falha de Tratamento , Resultado do TratamentoRESUMO
BACKGROUND: Previous studies suggested that methotrexate has beneficial effects in patients with Crohn's disease. We report our experience with this agent in patients with chronic active Crohn's disease who previously failed to improve with conventional treatment, including azathioprine in most cases. METHODS: Between June 1988 and June 1992, 39 patients with refractory Crohn's disease were treated with methotrexate. In patients with active disease, clinical remission was defined by a Harvey-Bradshaw index of less than 4. For patients also taking corticosteroids, the dates of remission and complete steroid withdrawal were recorded. For patients who achieved clinical remission, and those in clinical remission when methotrexate was started, the relapse rate on methotrexate therapy was noted. RESULTS: In the 37 patients with active disease at methotrexate initiation, the probability of remission was 72% at 3 months. The probability of remission and steroid withdrawal was 42% at 12 months. In patients on clinical remission, the probability of relapse on methotrexate was 58% at 12 months. Twenty-two patients experienced side-effects, but these only warranted methotrexate discontinuation in four cases. CONCLUSIONS: Methotrexate appears effective in most patients with refractory Crohn's disease and its short-term toxicity is acceptable, but the long-term benefit seems more limited.
Assuntos
Antimetabólitos/uso terapêutico , Doença de Crohn/tratamento farmacológico , Metotrexato/uso terapêutico , Adolescente , Corticosteroides/uso terapêutico , Adulto , Antimetabólitos/administração & dosagem , Resistência a Medicamentos , Feminino , Humanos , Injeções Intramusculares , Masculino , Metotrexato/efeitos adversos , RecidivaRESUMO
BACKGROUND: The efficacy of infliximab in ulcerative colitis (UC) and indeterminate colitis has been poorly assessed and preliminary results are conflicting. METHODS: The records of 30 patients treated with infliximab for ulcerative colitis (n=19) or indeterminate colitis (n=11) were reviewed. Infliximab was given because of steroid resistance (n=18), dependence (n=5) or intolerance (n=7); five patients had failed on cyclosporin; 19 patients had a severe flare-up. RESULTS: Median duration of follow-up was 10 months. In 28 patients with active disease, the response rate was 75% at day 7, with 43% having a complete remission, and 50% at month 1, with 32% having a complete remission. Among the 22 responders, the probability of relapse was 73% at month 6. The probability of complete remission without steroids, taking into account the re-treatment for relapse (n=11), was 57% (95% confidence interval (CI): 45% to 69%) at month 6. The probability of colectomy was 33% (95% CI: 23% to 43%) at month 12. In indeterminate colitis, response rate was only 50% at day 7 and 30% at month 1. Concomitant use of antimetabolite agents was associated with better results. CONCLUSIONS: Infliximab was able to induce a rapid response in some patients with UC or indeterminate colitis refractory to conventional treatment. Long-term results were less favourable, with frequent relapses, and about one-third of the patients required a colectomy.