RESUMO
OBJECTIVE: Ustekinumab (UST) is an anti-IL12/23 antibody for the treatment of Crohn's Disease (CD). The aim of this study was to compare the efficacy and safety of UST in a large population-based cohort of CD patients who failed previous treatment with other biologics. PATIENTS AND METHODS: 194 CD patients (108 males and 86 females, mean age 48 years (range 38-58 years) were retrospectively reviewed. 147 patients were already treated with anti-TNFα (75.8%), and 47 (24.2%) patients were already treated with anti-TNFα and vedolizumab. Concomitant treatment with steroids was present in 177 (91.2%) patients. RESULTS: At week 12, clinical remission was achieved in 146 (75.2%) patients. After a mean follow-up of 6 months, clinical remission was maintained in 135 (69.6%) patients; at that time, mucosal healing was assessed in 62 (31.9%) patients, and it was achieved in 33 (53.2) patients. Three (1.5%) patients were submitted to surgery. Steroid-free remission was achieved in 115 (59.3%) patients. Both serum C-Reactive Protein and Fecal Calprotectin (FC) levels were significantly reduced with respect to baseline levels during follow-up. A logistic regression, UST therapy as third-line therapy (after both anti-TNFα and vedolizumab), FC >200 µg/g, and HBI ≥8 were significantly associated with lack of remission. Adverse events occurred in 5 (2.6%) patients, and four of them required suspension of treatment. CONCLUSIONS: UST seemed to be really effective and safe in CD patients unresponsive to other biologic treatments, especially when used as second-line treatment.
Assuntos
Doença de Crohn/tratamento farmacológico , Ustekinumab/uso terapêutico , Adulto , Estudos de Coortes , Feminino , Humanos , Itália , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ustekinumab/administração & dosagem , Ustekinumab/efeitos adversosRESUMO
BACKGROUND AND AIMS: Our first objective was to evaluate the immune response to the adjuvanted 2009 A/H1N1 pandemic (pH1N1) vaccine in inflammatory bowel disease (IBD) patients treated with anti-TNF-α alone or combined with immunosuppressants (IS). Second and third aims were the safety of pH1N1 vaccine and the effects on IBD clinical activity. METHODS: 36 patients with Crohn's disease (CD) and 26 with ulcerative colitis (UC) and thirty-one healthy control (HC) subjects were enrolled. 47 patients were on anti TNF-α maintenance monotherapy and 15 on anti TNF-α combined with IS. Sera were collected at baseline (T0) and 4 weeks after the vaccination (T1) for antibody determination by hemagglutination inhibition (HAI). Disease activity was monitored at T0 and T1. RESULTS: Seroprotective titers (≥1:40) in patients were comparable to HC. Seroconvertion rate (≥4 fold increase in HAI titer) was lower than HC in IBD patients (p=0.009), either on anti TNF-α monotherapy (p=0.034) or combined with IS (p=0.011). Geometric mean titer (GMT) of antibodies at T1 was significantly lower in patients on combined therapy versus those on monotherapy (p=0.0017) and versus HC (p=0.011). The factor increase of GMT at T1 versus T0 was significantly lower in IBD patients versus HC (p=0.042), and in those on combined immunosuppression, both versus monotherapy (p=0.0048) and HC (p=0.0015). None of the patients experienced a disease flare. CONCLUSION: Our study has shown a suboptimal response to pH1N1 vaccine in IBD patients on therapy with anti TNF-α and IS compared to those on anti-TNF-α monotherapy and HC.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Colite Ulcerativa/imunologia , Doença de Crohn/imunologia , Imunossupressores/efeitos adversos , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/imunologia , Adalimumab , Adolescente , Adulto , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Antivirais/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Certolizumab Pegol , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Progressão da Doença , Quimioterapia Combinada , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Imunossupressores/uso terapêutico , Infliximab , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Several new biological drugs have been introduced in the last decade or are under investigation for the treatment of IBD. They include anti TNFalpha agents, anti adhesion molecules, anti IL-12/23, anti IL-6R and others. Their role in IBD therapy will be discussed in regard of the association of chronic inflammation and cancer in the gut. The risk of colorectal cancer is increased in ulcerative colitis (UC) and, to some extent, in Crohn's disease (CD). This association is well known from many years. However, the mechanisms linking chronic inflammation and carcinogenesis are beginning to be elucidated only recently. RESULTS AND CONCLUSIONS: Experimental data indicate that several cytokines could play a role in promoting tumour development. In this perspective, the anti cytokine agents could be not only powerful tools in treating inflammation but also efficacious in preventing the onset of inflammation associated colorectal cancer.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Doenças Inflamatórias Intestinais/terapia , Adalimumab , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Antineoplásicos/efeitos adversos , Certolizumab Pegol , Neoplasias Gastrointestinais/etiologia , Humanos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/patologia , Infliximab , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
In the last decade, biologic agents, in particular infliximab and adalimum-ab, have deeply changed the therapeutic armamentarium of inflammatory bowel disease (IBD). However, these drugs have a number of contraindications and side-effects that physicians should know so to avoid and eventually manage them. Another important issue is the early introduction of immunomodulators and biologics in the therapeutic algorithm of IBD, the so called "top-down" approach compared to the traditional "step-up" approach. In this review, the indications to the use of anti-TNF-alpha molecules in IBD are briefly reported and the potential benefits and disadvantages of a more aggressive approach are discussed.