Vedolizumabe comparado a agentes anti-TNF-α para indução e manutenção da remissão na doença de Crohn refratária a medicamentos biológicos: revisão rápida / Vedolizumab compared to anti-tnf-α agents for induction and maintenance of remission in biologic-refractory crohn's disease: a rapid review of systematic reviews

Vedolizumabe e anticorpos anti-TNF-α (infliximabe, adalimumabe, certolizumabe pegol). Indicação: Tratamento pessoas com doença de Crohn com falha a um agente biológico anti-TNF-α em tratamento prévio. Pergunta: Para adultos com doença de Crohn moderada a grave com falha terapêutica para anticorpos monoclonais anti-TNF-α, em tratamento de segunda linha, Vedolizumabe tem efeitos superiores aos anti-TNF-α para induzir e manter a remissão da doença? Objetivo: Investigar a eficácia e segurança do vedolizumabe, comparado aos agentes anti-TNF-α (infliximabe, adalimumabe, certolizumabe pegol), na indução e manutenção da remissão em pacientes refratários aos anti-TNF-α com doença de Crohn moderada a grave. Métodos: Revisão rápida de revisões sistemáticas. Levantamento bibliográfico foi realizado nas bases de dados PUBMED, EMBASE, SCOPUS, BVS, Cochrane Library e em registros de revisões sistemáticas e ensaios clínicos. Seguiu estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica dos estudos incluídos através da ferramenta AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version) Resultados: Foi selecionada uma revisão sistemática, que atendida aos critérios de elegibilidade, mas nenhum ensaio clínico foi escolhido, pois não atendiam aos critérios de inclusão. Conclusão: Adalimumabe, disponível no Sistema Único de Saúde, é mais eficaz que vedolizumabe para induzir remissão clínica em pacientes tratados previamente com biológicos. Vedolizumabe não é mais eficaz que placebo para induzir remissão clínica. Vedolizumabe e adalimumabe são similares entre si e são mais eficazes que placebo para manter a remissão clínica. Não foram encontradas evidências comparando vedolizumabe a infliximabe ou certolizumabe pegol

Vedolizumab and anti-TNF-α antibodies (infliximab, adalimumab, certolizumab pegol). Indication: Treatment of people with Crohn disease who have failed an anti-TNF-α biological agent in previous treatment. Question: For adults with moderate to severe Crohn disease with treatment failure for anti-TNF-α monoclonal antibodies, in second-line treatment, does vedolizumab have superior effects to anti-TNF-α in inducing and maintaining disease remission? Objective: To investigate the efficacy and safety of vedolizumab, compared to anti-TNF-α agents (infliximab, adalimumab, certolizumab pegol), in the induction and maintenance of remission in moderate to severe Crohn disease refractory to anti-TNF-α previous treatment. Methods: Rapid review of systematic reviews. A bibliographic search was done in the PUBMED, EMBASE, SCOPUS, BVS, Cochrane Library databases and in registries of systematic reviews and clinical trials. The search has followed predefined strategies. The methodological quality of the included studies was evaluated using the AMSTAR-2 tool (Assessing the Methodological Quality of Systematic Reviews Version 2). Results: A systematic review was selected, which met the eligibility criteria, but no clinical trials were chosen as they did not meet the inclusion criteria. Conclusion: Adalimumab, available in the Brazilian Public Health System, is more effective than vedolizumab to induce clinical remission in patients previously treated with biologics. Vedolizumab is no more effective than placebo in inducing clinical remission. Vedolizumab and adalimumab are similar to each other and are more effective than placebo in maintaining clinical remission. No evidence was found comparing vedolizumab to infliximab or certolizumab pegol

Quantitation of certolizumab pegol by validated liquid chromatography methods

Abstract Certolizumab pegol (CZP) is a Fab' fragment of the humanized antibody with anti-TNF-α activity that is indicated as therapy for Crohn's disease and rheumatoid arthritis. Using a BioSep-SEC-S3000 column (300 x 4.6 mm i.d., 5 µm particle size), a size exclusion liquid chromatography (SEC) method was developed. Mobile phase A consisted of 100 mM monobasic sodium phosphate and 200 mM sodium chloride (pH 7.0), while mobile phase B was ethanol (95:5, v/v), and the analysis was performed using a diode array detector (DAD) set to 214 nm and a flow rate of 0.5 ml min-1. In addition, a reversed-phase liquid chromatography (RP-LC) method based on gradient elution was developed on a Zorbax 300 SB C18 column (150 mm x 4.6 mm i.d., 3.5 µm particle size) kept at 80 °C. Mobile phase A was 0.1% (v/v) TFA in ultrapure water, and mobile phase B was a mixture of propanol, acetonitrile, ultrapure water and TFA (70 + 20 + 9.9 + 0.1, v/v) operated at a flow rate of 1.0 ml min-1, and DAD was applied at 214 nm. CZP elution was achieved with retention times of 5.6 min and 9.0 min for SEC and RP-LC, respectively.

Certolizumab Can Also Be Effective in Monotherapy for the Treatment of Rheumatoid Arthritis Patients.

OBJECTIVE: Although it is known that methotrexate (MTX) increases the effectiveness of biological drugs (mainly anti-TNFs) in patients with rheumatoid arthritis (RA), in real life, it is known that many patients using anti-TNFs are on monotherapy due to many causes. This article compares the effectiveness of certolizumab as monotherapy as combined with MTX or leflunomide (LFN) in RA patients with failure to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in a real-world setting. METHODS: A retrospective observational cohort study was conducted at a specialized centre for RA management in Colombia. Patients treated with certolizumab as monotherapy or in combination with MTX, LFN, or MTX+LFN, between 2011 and 2020 with a minimum 3-month follow-up were included. Demographics and RA clinical characteristics were recorded; effectiveness was assessed as the improvement in Disease Activity Score (DAS28) getting remission or low disease activity at 3, 6, and 12 months of treatment. RESULTS: A total of 181 patients were included, 24 received certolizumab as monotherapy, 62 certolizumab plus MTX, 47 certolizumab plus LFN and 48 certolizumab plus MTX+LFN. At 3 months of follow-up, 80% of the patients showed decreased disease activity, with no significant differences between groups; at 12 months of treatment, response in certolizumab monotherapy group was 94.4% compared to 81.8% in combination with MTX, 80.5% in combination with LFN and 51.4% in combination with MTX+LFN. Response at 3 months (OR 4.04; 95% CI 1.28-12.69) and positive anti-CCP (OR 3.83; 95% CI 1.11-13.21) were associated with 12-month response. CONCLUSION: Certolizumab seems to be effective as monotherapy in the treatment of RA patients with failure to csDMARDs.

FIRST LINE OF SUBCUTANEOUS ANTI-TNF THERAPY FOR RHEUMATOID ARTHRITIS: A PROSPECTIVE COHORT STUDY.

Objectives: This study aims to evaluate and compare the use of subcutaneous anti-TNF for RA in a Brazilian real-life setting. Methods: A prospective cohort of biological disease-modifying antirheumatic drug (bDMARD)-naïve patients treated with adalimumab, etanercept, golimumab, and certolizumab was developed. Medication persistence, disease activity by the Clinical Disease Activity Index (CDAI), functionality by the Health Assessment Questionnaire (HAQ), quality of life by the European Quality of Life 5 Dimensions (EQ-5D), and safety were evaluated at 6 and 12 months. Results: In a total of 327 individuals, 211 (64.5%) were persistent at 12 months. Patients improved after the use of anti-TNF, with a reduction in the mean of CDAI and HAQ, in addition to an increase in the mean of EQ-5D (p < 0.05). The number of patients who achieved the clinical response was 114 (34.86%) by CDAI, 212 (64.83%) by HAQ, and 215 (65.75%) by EQ-5D at 12 months. There were no statistically significant differences among the drugs (p > 0.05). The anti-TNF was well tolerated. Conclusion: Anti-TNF reduced disease activity, in addition to improving patients' functionality and quality of life. Additional pharmacotherapeutic monitoring can be essential to achieve better results.

Ameliorative effect of certolizumab on experimentally induced acute necrotic pancreatitis in rats

SUMMARY OBJECTIVE: The effects of Certolizumab, a pegylated monoclonal antibody to tumor necrosis factor α, on experimentally induced acute pancreatitis (AP) were examined. METHODS: Thirty-six Wistar Albino male rats were randomly divided into four groups. Group I was the control group and no medication administered to this group. Group II was the Certolizumab group, and 100 ml/kg serum physiologic administered into the biliopancreatic duct and a single dose of 10 μg Certolizumab was simultaneously administered intraperitoneally. Acute pancreatitis was induced with a retrograde injection of 3% Na taurocholate into the common biliopancreatic duct in the study (Group III) and treatment (Groups IV) groups. Rats were sacrificed 72 hours later. Serum amylase, lipase, lactate dehydrogenase activities, along with pancreatic histopathology, were examined. RESULTS: Certolizumab treatment significantly decreased serum amylase, lipase, and LDH levels; histopathologically edema, hemorrhage, parenchymal necrosis, fat necrosis, and infiltration scores; immunohistochemically MDA, MPO, TNF-α and Caspase-3 activity. CONCLUSION: The results support the idea that certolizumab might be beneficial for the severity of AP.

RESUMO OBJETIVO: Os efeitos de Certolizumab, um anticorpo monoclonal pegilado para o fator de necrose tumoral α, na pancreatite aguda induzida experimentalmente (PA) foram examinados. MÉTODO: Trinta e seis ratos Wistar Albino foram divididos aleatoriamente em quatro grupos. O Grupo I foi considerado o grupo controle e não recebeu medicação; o Grupo II foi o grupo Certolizumab e recebeu 100 ml/kg de soro fisiológico administrado no ducto biliopancreático e dose única de 10 mg Certolizumab administrada por via intraperitoneal simultaneamente. A pancreatite aguda foi induzida com uma injeção retrógrada de uma solução de 3% taurocolato de sódio aplicada no ducto biliopancreático comum nos grupos de estudo (Grupo III) e tratamento (Grupos IV). Os ratos foram sacrificados 72 horas depois. As atividades séricas de amilase, lipase, lactato desidrogenase, juntamente com a histopatologia pancreática, foram examinadas. RESULTADOS: O tratamento com Certolizumab diminuiu significativamente os níveis séricos de amilase, lipase e LDH; edema histopatológico, hemorragia, necrose paranquimatosa, necrose gordurosa e escores de infiltração; atividade imuno-histoquímica de MDA, MPO, TNF-α e Caspase-3. CONCLUSÃO: Estes resultados suportam a ideia de que o Certolizumab pode ser benéfico para a gravidade da PA.

Spotlight on certolizumab pegol in the treatment of axial spondyloarthritis: efficacy, safety and place in therapy.

Certolizumab pegol (CZP) is a pegylated humanized tumor necrosis factor-α inhibitor (TNFi) approved for the treatment of ankylosing spondylitis (AS) in the USA and for AS and non-radiographic axial spondyloarthritis (nr-axSpA) in Europe and in some Latin American countries. CZP lacks Fc region, preventing complement fixation and cytotoxicity mediated by antibody; CZP does not actively cross the placenta, unlike other TNFi. RAPID-axSpA study is a Phase III trial conducted in patients with AS and nr-axSpA as double blind and placebo controlled to week 24, dose blind to week 48 and open label to week 204. Of a total of 325 patients recruited, 107 patients were assigned to placebo and 218 patients to CZP (111 to CZP 200 mg Q2W, 107 to CZP 400 mg Q4W). Improvements in axial involvement, joint involvement, enthesitis and quality of life were reported in patients treated with CZP. Safety profile was like that reported for other TNFi in axSpA patients. In this article, we summarized the pharmacology and we reviewed the efficacy and tolerability of this drug for the treatment of axSpA. Some special considerations of CZP during pregnancy are included. CZP, the latest TNFi to be approved, showed efficacy in all manifestations of AS and nr-axSpA.

Certolizumab pegol in a heterogeneous population of patients with moderate-to-severe rheumatoid arthritis.

AIM: To determine the efficacy and safety of certolizumab pegol for the treatment of rheumatoid arthritis in a real-world setting. MATERIALS & METHODS: Patients with moderate-to-severe rheumatoid arthritis who initiated therapy with certolizumab were followed for 12 weeks. Response was assessed with Disease Activity Score of 28 joints, European Ligue Against Rheumatism criteria and Simplified Disease Activity Index. Predictors of response were analyzed with binary logistic regression models. RESULTS: Statistically significant decreases in tender and swollen joint counts, laboratory parameters and use of corticosteroids and disease-modifying antirheumatic drugs were found. Disease activity also significantly diminished. Higher Disease Activity Score of 28 joints at baseline was the main predictor of response. No severe adverse events were reported. CONCLUSION: Certolizumab was effective and well tolerated, particularly in the subpopulation with higher inflammatory burden at baseline.

Cost-minimization and budget impact analysis of certolizumab pegol for patients with Crohn's disease, moderate or severe, with relapse after conventional treatment from the perspective of the Brazilian private payer / Análises de custo-minimização e impacto orçamentário do certolizumabe pegol para pacientes com doença de Crohn moderada a grave com falha ao tratamento convencional, sob a perspectiva do pagador privado no Brasil

Objectives: Budget impact and cost-effectiveness analysis are often required by payers when discussing drug reimbursement. We hereby present a cost-minimization (CMA) and budget impact analysis (BIA) regarding the incorporation of certolizumab pegol (CZP) for the treatment of patients with Crohn's disease, a debilitating condition that affects the digestive tract. Methods: Considering that the scientific literature demonstrates CZP as effective as the alternatives (infliximab and adalimumab), a CMA was conducted, including a Markov 10-year time horizon modeling. Focusing on the assumptions for both CMA and BIA, a total of 36 stakeholders from the private sector were surveyed regarding treatment and disease-related costs. For the BIA, drug acquisition costs, administration costs, no population growth and an immunobiologic drug (bDMARD) switching rate of 5% were also considered. We assumed that CZP would gradually gain market share until it reaches 20% of new or switching patients in the fourth year. In addition, probability sensitivity analyses were performed. Results: In the cost-minimization, the calculated costs for 10-year treatment were BRL149k (infliximab); BRL118k (adalimumab) and BRL83k (CZP). Probabilistic sensitivity analysis was conducted with 1,000 random simulations, with CZP being less costly than its comparators in all simulations. Additionally, the BIA result indicates that CZP is a cost-saving intervention, with a predicted five-year impact of BRL317k for every 100-patient cohort. Conclusions: Certolizumab pegol was shown to be not only effective but also a cost-saving drug when compared to other anti-TNF drugs available for the Brazilian private healthcare system.

Objetivos: Análises de impacto orçamentário e de custo-efetividade são, com frequência, exigidas por pagadores para a decisão sobre incorporação de drogas. Por esse motivo, apresentaremos uma análise de custo-minimização e de impacto orçamentário do certolizumabe pegol (CZP) para o tratamento de pacientes com doença de Crohn, doença crônica e debilitante que afeta o trato digestivo. Métodos: Trinta e seis pagadores privados foram entrevistados para que fosse possível compreender os custos de tratamento e aqueles relacionados à doença. Para a análise de impacto orçamentário, foram assumidos: custos de aquisição e administração das drogas, nenhuma taxa de crescimento populacional, taxa de troca de medicamento biológico (bDMARD) de 5% e market share de 20% para o CZP em seu pico. Visto que o CZP é tão eficaz e seguro quanto os comparadores disponíveis, optou-se pela análise de custo-minimização, assumindo horizonte temporal de 10 anos. Resultados: A análise de impacto orçamentário mostra que o CZP é capaz de gerar redução de custos no valor de R$ 317 mil em cinco anos, para cada cem pacientes. Para a custo-minimização, os custos calculados no horizonte de dez anos foram: R$ 149 mil para o infliximabe; R$ 118 mil para o adalimumabe e R$ 83 mil para o CZP. A análise de sensibilidade probabilística mostrou CZP menos custoso em 100% das 1.000 simulações. Conclusões: Certolizumabe pegol mostrou-se não apenas efetivo, mas também uma opção que pode gerar redução de custos quando comparada às outras drogas biológicas no Brasil sob a perspectiva do pagador privado.

An evidence-based review of certolizumab pegol in the treatment of active psoriatic arthritis: place in therapy.

Certolizumab pegol (CZP) is a pegylated humanized tumor necrosis factor-α inhibitor (TNFi) approved for the treatment of psoriatic arthritis (PsA) in Europe, the USA, and Latin American countries. CZP neutralizes TNF-α at its soluble and membrane portions. Due to the lack of Fc region, it does not induce complement or antibody-dependent cytotoxicity in vitro, unlike other TNFi. RAPID-PsA study, the only randomized clinical trial performed in PsA, is a Phase III clinical trial conducted in 409 PsA patients during 24 weeks. Patients were randomized to CZP (200 mg every 2 weeks or 400 mg every 4 weeks) or placebo. Patients in CZP arms reported improvements in skin disease, joint involvement, dactylitis, enthesitis, and quality of life. Safety profile was similar to that reported for other TNF-α inhibitors in PsA patients. This article summarizes the pharmacology and reviews the efficacy and tolerability of this drug in PsA. CZP is the newest TNFi with proved efficacy in all manifestations of psoriasis disease, except for axial involvement where the evidence has been derived from response to axial spondyloarthritis.

Biologic therapy for refractory scleritis: a new treatment perspective.

Scleritis is an umbrella term for a heterogeneous group of ocular diseases that can be associated with autoimmune or systemic disorders. The purpose of this article was to review the literature regarding the use of biologic drugs to treat refractory scleritis. A search of the MEDLINE, Embase, and LILACS electronic databases was conducted, and the reference lists of published articles were hand-searched. No language filters were used. This search strategy yielded no randomized trials of the use of biologic therapies to treat scleritis; only case reports and retrospective studies were retrieved. These studies suggest that monoclonal antibodies (infliximab and adalimumab) are superior to the soluble TNF receptor fusion protein etanercept for the treatment of scleritis in patients that do not respond to corticosteroids and/or to immunosuppressive treatment. Rituximab seems to be the best option for scleritis associated with vasculitis.

Tratamiento exitoso con certolizumab pegol en un paciente con enfermedad de Crohn fistulizante compleja / Severe fistulizing crohn’s disease successfully treated with certolizumab pegol

Crohn’s disease (CD) is a type of inflammatory bowel disease that may involve every segment of the entire gastrointestinal tract and is characterized by transmural inflammation and formation of granulomas. Its classic presentation is evidenced by fever, abdominal pain and signs of intestinal obstruction, however these signs could vary among patients. Fistulizing CD (FCD) is a less frequent presentation. The clinical signs and symptoms of this form are not characteristic and usually have a more complicated outcome due to the development of sepsis. Certolizumab pegol is a recombinant humanized antibody, targeting the tumor necrosis factor alpha (TNF-alpha), which has been effective in patients with fistulizing CD. In this article, we report a patient with complicated FCD who required 21 month hospitalization due to the presence of multiple fistulae and malnutrition, but who had a successful management with certolizumab pegol.

La enfermedad de Crohn (EC) es un tipo de enfermedad intestinal inflamatoria, que puede comprometer cualquier segmento del tracto gastrointestinal caracterizado por inflamación transmural y formación de granulomas. Su presentación clínica clásica se caracteriza por fiebre, dolor abdominal y signos de obstrucción intestinal, aunque estos signos pueden variar entre cada paciente. La EC fistulizante (ECF) es un tipo de presentación menos frecuente. Los síntomas y signos clínicos no son fácilmente definidos y usualmente se asocian con el desarrollo de sepsis. El certolizumab pegol es un anticuerpo monoclonal recombinante contra el factor de necrosis tumoral alfa. En este artículo se describe la evolución clínica de un paciente con ECF con múltiples complicaciones y quien requirió una hospitalización prolongada durante 21 meses debido a la presencia de múltiples fístulas y desnutrición, quien respondió satisfactoriamente al tratamiento con certolizumab pegol.

Aplicación práctica del uso de la terapia anti-TNF en la enfermedad de Crohn: ¿Cuándo comenzar, cuál elegir, cómo predecir la respuesta, cuándo cambiar y cuándo suspender? / Practical application of anti-TNF therapy for luminal Crohn`s disease: when to start, which drug to choose, how to predict response,when to change and when to stop?

Anti-tumor necrosis factor (anti-TNF) therapy has been an important step in the management of inflammatory bowel disease. These drugs proved to reduce the need for both hospitalization and surgery in Crohn`s disease patients. In consideration of high economic cost and safety issues there is the need to have clear recommendations for their use. Better patient selection might maximize the clinical benefit for those in most need of an effective therapy to avoid disabling disease, whilst also minimizing the complications associated with therapy. All biological drugs are potentially immunogenic and this can be reduced by combination with immunomodulators. However, the balance of risk and benefit of this strategy must be judged for individual patients. Further, the measurement of levels and anti-drug antibodies for these drugs may help to optimize therapy and to avoid loss of response. Finally, in some patients an appropriate strategy for stopping biological treatment is possible.

La terapia biológica anti-factor de necrosis tumoral (anti-TNF) ha sido un importante avance en el manejo de las enfermedades inflamatorias intestinales. Estos fármacos han demostrado reducir la necesidad de hospitalización y cirugía en pacientes con Enfermedad de Crohn. En consideración a su alto costo económico y su seguridad, es necesario tener claro las recomendaciones sobre su uso. Una mejor selección de los pacientes puede maximizar el beneficio clínico de aquéllos que requieren una terapia más efectiva, para evitar la evolución hacia una enfermedad más discapacitante, mientras minimizamos las complicaciones asociadas a esta terapia. Todos los fármacos biológicos son potencialmente inmunogénicos y esto puede ser reducido con la combinación con inmunomoduladores. Sin embargo, el balance entre los riesgos y beneficios de esta estrategia debe ser evaluado para cada paciente en particular. Por otra parte, la medición de los niveles y los anticuerpos para estos fármacos puede ayudar a optimizar la terapia, evitando la pérdida de respuesta. Finalmente, una apropiada estrategia de suspensión de la terapia biológica es posible en algunos pacientes.

Prefilled certolizumab pegol (Cimzia(®)) syringes for self-use in the treatment of rheumatoid arthritis.

A new anti-tumor necrosis factor alpha (TNF-α) inhibitor with a novel mechanism of action has entered phase 3 trials in rheumatoid arthritis (RA). Certolizumab pegol (Cimzia(®)) is a humanized Fab' antibody fragment against TNF-α with a polyethylene glycol tail that prevents complement-dependent and antibody-dependent cell-mediated cytotoxicity or apoptosis. Four randomized clinical trials have been published so far. Reported results are similar to those published in previous studies with other TNF-α inhibitors, with ACR20, ACR50, and ACR70 responses of around 60%, 40%, and 20%, respectively, when combined with methotrexate and slightly lower when used as monotherapy. Safety was shown to be similar to that seen with TNF-α blockers and some cases of tuberculosis were seen in the trials, stressing the importance of a complete screening in these patients. Although we still need effectiveness and safety data in larger numbers of patients and longer follow-up, this new TNF inhibitor is a welcome addition to our current armamentarium for the treatment of RA.

Tratamiento con agentes anti-TNFα en la enfermedad de Crohn: ¿qué fármaco debemos utilizar y cuándo?: [revisión] / Treatment with anti-TNFα agents in Crohn's disease: what drug we have to use and when?: [revision]

Crohn's disease (CD) is often very difficult to treat. Almost ten years ago "biologic" agents were introduced in the armamentarium to control CD. Although there are many new drugs in the pipeline, only two antiTNF agents have been released to the market (infliximab and, recently, adalimumab) and probably in 2008 certolizumab will be approved. A review of available evidence suggests that the three antibodies are effective in the induction and maintenance of response, and (to a lesser extent) remission. Infliximab has been very useful in fistulizing disease, and preliminary data do suggest that adalimumab and certolizumab will be also. Cost and long-term safety limit the use of these agents in daily practice. To maximize benefits and minimize risks, good patient selection and strict adherence to Clinical Guidelines seem the key points. It has been suggested that these drugs should be used in early disease to avoid progression, but current data are very scarce to generalize this recommendation. In anycase, we think that the use of "biologics" will provoke a dramatic change in CD treatment in the next 10 years.

Crohn’s disesae (CD) is often very difficult to treat. Almost ten years ago "biologic" agents were introduced inthe armamentarium to control CD. Although there are many new drugs in the pipeline, only two antiTNF agents have been released to the market (infliximab and, recently, adalimumab) and probably in 2008 certolizumabwill be approved. A review of available evidence suggests that the three antibodies are effective in the induction and maintenance of response, and (to alesser extent) remission. Infliximab has been very useful in fistulizing disease, and preliminary data do suggest that adalimumab and certolizumab will be also. Cost and long-term safety limit the use of these agents in daily practice. To maximize benefits and minimize risks, good patient selection and strict adherence to Clinical Guidelines seem the key points. It has been suggestedthat these drugs should be used in early disease to avoid progression, but current data are very scarce to generalize this recommendation. In anycase, we think that the use of "biologics" will provoke a dramaticchange in CD treatment in the next 10 years.