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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
Subject(s)
Humans , Male , Female , Crohn Disease/drug therapy , Certolizumab Pegol/therapeutic use , Adalimumab/therapeutic use , Infliximab/therapeutic use , Health StrategiesABSTRACT
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.
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Objective:To evaluate the efficacy of certolizumab pegol (CZP) in the treatment of Chinese women of childbearing age with inflammatory joint diseases and the effect of intrauterine exposure on infant vaccination and risk of infection.Methods:This study is a retrospective observation study, including female patients of childbearing age who were treated with CZP in the outpatient clinic from November 2019 to October 2020. The patients were followed up for 24 weeks, and the related data was collected. We adopted disease activity score-28 for rheumatoid arthritis with CRP (DAS28-CRP), clinical disease activity index (CDAI) and simplified disease activity index (SDAI) to evaluate disease activity. Bath ankylosing spon-dylitis disease activity index (BASDAI) and ankylosing spondylitis disease activity score (ASDAS-ESR) were used to assess the disease activity of patients with ankylosing spondylitis or spondyloarthritis (AS/SpA). Low disease activity (LDA), the dosage of glucocorticoid (GC) and the qualified rates of ACR20 and ASAS20 were calculated to validate the efficacy of CZP. The data of infants vaccination and infection was recorded to estimate the effect of intrauterine exposure on infants. Correlation analysis were performed using paired t test or Mann Whitney test. All statistical tests were bilateral, with a significance of P<0.05. Results:Twenty women entered the study and fifteen completed, including eight patients with RA, six patients with AS and 1 patient with SpA. The average age was (30±5) years and the median symptom duration was 5.0 (3.0, 6.5) years. When these RA patients were enrolled into the study, DAS28-CRP, CDAI and SDAI were (3.4±1.2), 15.5(9.5, 21.0) and (18±12) respectively; and after the use of CZP, the DAS28-CRP, CDAI and SDAI changed to (2.5±0.9)( t=2.48, P=0.042), 4.5(3.5, 10.8) ( U=12.50, P=0.040) and (9±6) (t=2.76, P=0.028). At the first follow-up, the ACR20 rate was 50%. and at the end of the study, the LDA rate was 75%(6/8), three(37.5%) women reduced the dosage of GC. Among the AS/SpA patients, BASDAI was 19.0(14.5, 26.0) and ASDAS-ESR was (2.4±1.0) at first, while after treatment, BASDAI turned into 9.0(1.0, 10.5) ( U=11.50, P=0.100) and ASDAS-ESR turned into (1.4±0.5) ( t=3.44, P=0.014). The ASAS20 rate at the first follow-up was 71.4%(5/7), and 85.7%(6/7) at the end of the study. Four patients experienced adverse events, resulting in drug withdrawal. Three women were pregnant when they were enrolled into the study, and three others became pregnant during the research. Six infants were vaccinated with live attenuated vaccines and inactivated vaccines according to the plan. No adverse event related to vaccination was reported, but one of the babies had perianal abscess and the other one had cold symptoms, while both improved after treatment. Conclusion:CZP can effectively control disease activity of women with inflammatory joint diseases during pregnancy, and intrauterine exposure is safe to infants during the study period.
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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.
Subject(s)
Animals , Rats , Pancreatitis, Acute Necrotizing/drug therapy , Certolizumab Pegol/therapeutic use , Immunosuppressive Agents/therapeutic use , Taurocholic Acid , Rats, Wistar , Pancreatitis, Acute Necrotizing/chemically induced , Pancreatitis, Acute Necrotizing/pathology , Disease Models, AnimalABSTRACT
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.
Subject(s)
Humans , Biological Products , Crohn Disease , Technology Assessment, BiomedicalABSTRACT
Objective:To explore the efficacy and safety of Certolizumab pegol in patients with rheumatoid arthritis. Methods:Such databases as Pubmed, Medline, Embase, The Cochrane Library, WANFANG, CNKI, Science, CBM and VIP were searched from their establishment to March 2015 for collecting the randomized controlled trials comparing Certolizumab pegol and placebo in the treatment of RA. The meta-analysis was undertaken using RevMan5. 3 for Windows. Results:Ten publications and eight researches met the inclusion criteria with high quality. The results revealed CZP significantly improved the ACR20,ACR50,ACR70 response rates,and physical function. CZP was associated with a statistically significant reduction in Disease Activity Score in 28 joints-Erythrocyte sedimentation rate, arthritis pain, and fatigue. There were no significant differences of incidence of treatment-related adverse events between CZP group and placebo group. Conclusion:CZP significantly reduced the RA signs and symptoms,improved physical function and life quality as compared with the placebo in the treatment of RA. More large-scale RCTs are needed to evaluate the long-term efficacy and safety of CZP in the treatment of RA.
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Crohns 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.