RESUMO
AIM: To identify factors predicting mucosal healing in ulcerative colitis patients treated with anti-TNFα agents with or without azathioprine. METHODS: In a prospective, multicenter, one-year study biologic naïve patients aged 25-65 years, with corticosteroid-dependent or refractory colitis received combination treatment with anti-TNFα and azathioprine for 6 months followed by anti-TNFα monotherapy. Patients who denied combination therapy or were outside this age range received anti-TNFα monotherapy (controls). Before and at weeks 12 and 54 of treatment the total Mayo score was calculated. Mucosal healing was defined as endoscopic subscore of 0. Mucosal expression of T helper (Th) cell-lineage specific transcription factors (Tbet, Gata3, Rorc, FoxP3) before treatment was also associated with mucosal healing. RESULTS: Of 67 patients, 58 (86.6%) received combination and 9 (13.4%) anti-TNFα monotherapy. Overall 29 (43.3%) patients achieved mucosal healing; rates were higher in patients receiving combination therapy vs. monotherapy (p=0.03) and in azathioprine naïve vs. exposed patients in the combination group (p=0.01). Mucosal healing was associated with lower pre-treatment mucosal expression of transcription factor Th1-Tbet (p<0.05) and higher expression of Th17-Rorc (p<0.05). CONCLUSIONS: Mucosal healing was associated with combination therapy, especially in biologic and azathioprine-naïve patients and pre-treatment mucosal expression of specific Th specific transcripting factors (Tbet and Rorc).
Assuntos
Adalimumab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Azatioprina/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Imunossupressores/uso terapêutico , Infliximab/uso terapêutico , Adulto , Idoso , Colonoscopia , Quimioterapia Combinada , Feminino , Grécia , Humanos , Mucosa Intestinal/efeitos dos fármacos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Estudos Prospectivos , Índice de Gravidade de Doença , Proteínas com Domínio T/metabolismo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , CicatrizaçãoRESUMO
BACKGROUND AND AIMS: Extraintestinal manifestations [EIMs] are common in inflammatory bowel disease [IBD]. Data on epidemiology and risk factors of EIMs in IBD patients are limited. The aim of this study was to investigate the prevalence of EIMs in a large cohort of Greek IBD patients and identify risk factors for their development. METHODS: The study population consisted of IBD patients, who were followed in eight tertiary Greek hospitals. Demographic and clinical characteristics of patients were analysed. The diagnosis of EIMs was based on standard criteria and on specialist consultation. RESULTS: In total, 1860 IBD patients (1001 with Crohn's disease [CD], 859 with ulcerative colitis [UC]) were registered. Among them 615 [33.1%] exhibited at least one EIM; 238 patients [38.6%] developed an EIM before IBD diagnosis. An association between active IBD and presence of an EIM was established in 61.1% of the patients. Arthritic [peripheral arthritis], mucocutaneous [erythema nodosum], and ocular [episcleritis] were the most common manifestations. EIMs were more prevalent in females, patients with CD, smokers [for all p <0.0001], patients with extensive UC [p = 0.007], and patients with a previous appendectomy [p < 0.0001] or a major IBD-related surgery [p = 0.012]. CONCLUSIONS: About one-third of Greek IBD patients developed at least one EIM. Of those, more than one-third had their EIM diagnosed before IBD, and in about two-thirds it was related to disease activity. EIMs were more frequently present in females and patients with extensive UC in multivariate analysis.
Assuntos
Doenças Inflamatórias Intestinais/epidemiologia , Adulto , Artrite/epidemiologia , Artrite/etiologia , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/patologia , Doença de Crohn/epidemiologia , Doença de Crohn/patologia , Eritema Nodoso/epidemiologia , Eritema Nodoso/etiologia , Feminino , Grécia/epidemiologia , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Esclerite/epidemiologia , Esclerite/etiologia , Fatores Sexuais , Adulto JovemRESUMO
OBJECTIVES: A high proportion of Crohn's disease (CD) patients lose response to antitumor necrosis factor (anti-TNF) and therapy needs to be intensified. We aimed to prospectively determine the predictors and frequency of anti-TNF loss of response and therefore the need for dose escalation and de-escalation in CD patients treated with infliximab or adalimumab. METHODS: All patients were anti-TNF naive while concomitant azathioprine was administered for 6 months. In patients initially responding to anti-TNF and subsequently losing clinical response after the first 14 weeks of therapy, dose escalation was scheduled. During the follow-up period and after 1 year of intensified administration, anti-TNF was de-escalated in patients in remission. RESULTS: A total of 161 patients were started on infliximab (n=96) or adalimumab (n=65); however, 29 patients (18.0%) did not respond to therapy and were excluded from further analysis. From the remaining 132 patients (infliximab=77, adalimumab=55), 31 (23.5%) needed a dose escalation for maintenance of remission during a median 28-month follow-up period. Factors associated with loss of response and therefore the need for anti-TNF dose escalation were azathioprine discontinuation earlier than 6 months and smoking. Most patients achieved clinical remission (n=25, 80.6%) without other interventions and among these, 16 patients (64%) were successfully de-escalated to the standard maintenance infliximab or adalimumab dose schedule after 1 year of intensified anti-TNF administration. CONCLUSION: Azathioprine discontinuation earlier than 6 months and smoking in CD patients started on anti-TNF therapy is associated with loss of response and the need for anti-TNF dose escalation.
Assuntos
Adalimumab/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Azatioprina/administração & dosagem , Doença de Crohn/tratamento farmacológico , Imunossupressores/administração & dosagem , Infliximab/administração & dosagem , Adalimumab/uso terapêutico , Adulto , Anti-Inflamatórios/uso terapêutico , Azatioprina/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Quimioterapia de Indução/métodos , Infliximab/uso terapêutico , Quimioterapia de Manutenção/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND-AIM: The aim of this study is to identify the long term benefit of one year infliximab administration for the treatment of chronic refractory pouchitis following ileo-pouch anal anastomosis (IPAA) for ulcerative colitis (UC). METHODS: Seven patients with chronic refractory pouchitis diagnosed by clinical, endoscopic and histological criteria received infliximab 5 mg/kg at 0, 2, and 6 weeks and thereafter every 2 months for 1 year. Three patients had fistulae (1 pouch-bladder, 2 perianal) and 4 extraintestinal manifestations (2 erythema nodosum, 2 arthralgiae). All patients were refractory to antibiotics and 3 to azathioprine. Crohn's disease was excluded after re-evaluation of the history and small bowel examination with enteroclysis or capsule endoscopy. Clinical response was classified as complete, partial and no response. Fistulae closure was classified as complete, partial and no closure. The pouchitis disease activity index (PDAI) was used as an outcome measure. All patients were followed up for 3 years after discontinuation of infliximab therapy. RESULTS: After 1 year of infliximab administration 5 patients had complete clinical response, 1 partial clinical response and 1 no response, while 2 out of the 3 patients with fistulae had a complete closure. The median PDAI dropped from 11 (baseline) (range, 10-14) to 5 (range, 3-8). Extraintestinal manifestations were in complete remission too. Three years after completion of therapy, all patients with complete clinical response at one year remained in remission. CONCLUSIONS: One year infliximab administration is associated with a long term benefit in patients with chronic refractory pouchitis following IPAA for UC.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Fístula Cutânea/complicações , Fístula Intestinal/complicações , Pouchite/tratamento farmacológico , Fístula da Bexiga Urinária/complicações , Adulto , Artralgia/complicações , Artralgia/tratamento farmacológico , Doença Crônica , Colite Ulcerativa/cirurgia , Bolsas Cólicas/efeitos adversos , Bolsas Cólicas/patologia , Fístula Cutânea/tratamento farmacológico , Eritema Nodoso/complicações , Eritema Nodoso/tratamento farmacológico , Feminino , Humanos , Infliximab , Fístula Intestinal/tratamento farmacológico , Masculino , Pouchite/complicações , Índice de Gravidade de Doença , Fatores de Tempo , Fístula da Bexiga Urinária/tratamento farmacológicoRESUMO
AIM: To determine the efficacy of infliximab in the treatment of chronic refractory pouchitis, following ileo-pouch anal anastomosis (IPAA) for ulcerative colitis (UC). METHODS: Seven patients (4 females, 3 males) with chronic refractory pouchitis were included in an open study. Pouchitis was diagnosed by clinical plus endoscopic and histological criteria. Three patients also had fistulae (pouch-bladder in 1 and perianal in 2). Extraintestinal manifestations were also present in 4 patients (erythema nodosum in 2, arthralgiae in 2). All patients were refractory to standard therapy. Crohn's disease was carefully excluded in all patients after re-evaluation of the history and examination of the small bowel with enteroclysis or small bowel capsule endoscopy. Patients received Infliximab 5 mg/kg at 0, 2 and 6 weeks and thereafter every 2 months for 1 year. Clinical response was classified as complete, partial, and no response. Fistulae closure was classified as complete, partial, and no closure. The pouchitis disease activity index (PDAI) was also used as an outcome measure. RESULTS: Clinically, all patients improved. After 1 year of follow-up, 5 of the 7 patients had a complete clinical response, and 2 of the 3 patients with a fistula had complete fistulae closure. At the end of the follow-up period the median PDAI dropped from 11 (baseline) (range, 10-14) to 5 (range, 3-8). Extraintestinal manifestations were in complete remission at the end of the followup period as well. CONCLUSIONS: Our results indicate that infliximab may be recommended for the treatment of chronic refractory pouchitis complicated or not by fistulae following IPAA for UC.