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1.
Aliment Pharmacol Ther ; 59(12): 1579-1588, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38616417

RESUMO

BACKGROUND: Few data are available addressing the impact of post-operative management of Crohn's disease (CD) on long-term clinical course. AIM: To assess the evolution of post-operative management strategies over the last 40 years and their impact on the re-operation rate of CD. METHODS: We included 657 patients with CD who had undergone their first radical ileo-caecal resection between 1980 and 2020. Three cohorts were defined according to year of surgery: cohort 1 (1980-1998; n = 198), cohort 2 (1999-2009; n = 218) and cohort 3 (2010-2020; n = 241). We estimated exposure to immunomodulators and anti-TNFα agents after surgery and rates of re-operation using Kaplan-Meier survival analyses. We used Cox proportional hazards regression to assess the association of clinical variables with time to re-operation. RESULTS: Immunosuppressants, (IMMs) and anti-TNFα exposure within 5 years after surgery increased significantly from cohort 1 to cohort 2 and cohort 3 (IMMs: 1.6%, 38.2% and 28.0%, respectively, p < 0.001; anti-TNFα: 0.0%, 20.7% and 52.0%, respectively, p < 0.001). There was no significant difference across cohorts regarding the cumulative probability of re-operation within 5 and 10 years. Multivariate analysis identified IMMs/anti-TNFα exposure before the first surgery (HR 9.15; 95% CI 2.77-30.21) and post-operatively (HR: 0.24; 95% CI 0.07-0.74) as variables associated with the risk of re-operation. However, these associations had a time-varying effect and become non-significant after 5 and 2 years after surgery, respectively. CONCLUSION: Despite increased post-operative use of IMMs and anti-TNFα agents in the last two decades, the impact of these strategies on the risk of long-term re-operation rate has been modest.


Assuntos
Doença de Crohn , Reoperação , Humanos , Doença de Crohn/cirurgia , Doença de Crohn/tratamento farmacológico , Feminino , Masculino , Reoperação/estatística & dados numéricos , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Imunossupressores/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Cuidados Pós-Operatórios/métodos , Adulto Jovem , Estimativa de Kaplan-Meier , Fatores de Tempo , Modelos de Riscos Proporcionais
2.
Dig Dis Sci ; 69(5): 1785-1792, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38530500

RESUMO

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor recently approved to induce and maintain remission in ulcerative colitis (UC). AIMS: Considering the number of anti-TNF non-responders, this study aims to assess the effectiveness and safety of tofacitinib in a cohort of multi-failure patients with moderate-to-severe UC at 52 weeks. METHODS: From January 2021 to March 2023, we performed a prospective multicenter study observing adult patients with moderate-to-severe UC starting tofacitinib after an anti-TNF failure for a 52-week-long period. Effectiveness and safety were assessed in terms of colectomy rate, clinical remission and response, endoscopic remission, steroid-free clinical remission, and rate of adverse events. RESULTS: We included 58 patients with UC with an age of 42 ± 14.4 years, 59% males, 96.6% left-sided or pancolitis, who were failure to a single (65.5%) or more than one anti-TNF (34.5%). Only 6 (10.3%) patients underwent colectomy. Colectomy was clinically associated with the necessity and the number of extra cycles of tofacitinib 10 mg bid at W8 (p = 0.023) and W24 (p = 0.004), and with a higher partial Mayo score at W8 (p = 0.025). At W52, clinical remission, clinical response, and steroid-free clinical remission were 53.4%, 43.1%, and 48.3%, respectively. Of 22 performed colonoscopies at W52, 11 (50%) showed endoscopic remission. Adverse events occurred in 14 (24.1%) patients, but only 2 (3.4%) led to tofacitinib discontinuation. CONCLUSIONS: In a real-life setting of patients with anti-TNF refractory UC, tofacitinib has proved to be effective in preventing colectomy and inducing clinical and endoscopic remission at 52 weeks with a good safety profile.


Assuntos
Colectomia , Colite Ulcerativa , Piperidinas , Pirimidinas , Humanos , Colite Ulcerativa/cirurgia , Colite Ulcerativa/tratamento farmacológico , Pirimidinas/uso terapêutico , Masculino , Feminino , Colectomia/efeitos adversos , Piperidinas/uso terapêutico , Piperidinas/efeitos adversos , Piperidinas/administração & dosagem , Adulto , Pessoa de Meia-Idade , Estudos Prospectivos , Itália/epidemiologia , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Inibidores de Janus Quinases/uso terapêutico , Inibidores de Janus Quinases/efeitos adversos , Indução de Remissão , Resultado do Tratamento , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos
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