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1.
BMJ Case Rep ; 14(1)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514619

RESUMO

We report the case of a 43-year-old man, suffering from ankylosing spondylitis and treated with Infliximab 5 mg/kg every 2 months, with an excellent disease control. During a follow-up consultation, an incipient renal insufficiency is detected. A urine analysis showed haematuria and proteinuria and a renal puncture-biopsy revealed an image of IgA nephropathy.Several cases of IgA nephropathy have been reported in the literature associated with ankylosing spondylitis. Some of them occur in patients treated with antitumour necrosis factor, but it is unclear whether this pathology is caused by the treatment or whether treatment failed to prevent its occurrence.Our clinical case highlights the importance of regular monitoring of renal function in patients with ankylosing spondylitis, as well as urinary spotting.The question of whether the disease itself, the treatment or other factors such as immune dysregulation could be held responsible for kidney disease will be addressed in the discussion.


Assuntos
Antirreumáticos/uso terapêutico , Glomerulonefrite por IGA/patologia , Infliximab/uso terapêutico , Espondilite Anquilosante/complicações , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Antirreumáticos/administração & dosagem , Biópsia , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/urina , Hematúria/diagnóstico , Humanos , Infliximab/administração & dosagem , Rim/patologia , Testes de Função Renal/normas , Masculino , Monitorização Fisiológica/normas , Proteinúria/diagnóstico , Remissão Espontânea , Espondilite Anquilosante/tratamento farmacológico
3.
BMJ Case Rep ; 13(12)2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33370944

RESUMO

A 59-year-old man with refractory Cronkhite-Canada syndrome (CCS) had poor clinical response to high-dose intravenous steroids, azathioprine, total parenteral nutrition and best supportive care. He remained highly symptomatic with abdominal pain, diarrhoea, recurrent sepsis and profound weight loss. Infliximab induction was given as rescue therapy, with marked clinical improvement observed within 3 weeks. This allowed steroid taper. Within 12 months of infliximab therapy, he achieved complete clinical remission and returned to his baseline weight and a full oral diet. Sequential endoscopies observed significant regression of previous marked gastrointestinal polyposis, including histological remission on colonic biopsies at 3.5 and 5 years of treatment. He currently remains in remission following 6 years of combination therapy with 5 mg/kg 8 weekly infliximab and azathioprine, and there is ongoing discussion with regard to the benefits and risks of therapy de-escalation. This case demonstrates the effectiveness of infliximab in inducing and maintaining remission in refractory CCS.


Assuntos
Fármacos Gastrointestinais/uso terapêutico , Imunossupressores/farmacologia , Infliximab/uso terapêutico , Polipose Intestinal/tratamento farmacológico , Azatioprina/farmacologia , Azatioprina/uso terapêutico , Colo/diagnóstico por imagem , Colo/patologia , Colonoscopia , Resistência a Medicamentos , Fármacos Gastrointestinais/farmacologia , Gastroscopia , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Quimioterapia de Indução/métodos , Infliximab/farmacologia , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Polipose Intestinal/diagnóstico , Masculino , Pessoa de Meia-Idade , Antro Pilórico/diagnóstico por imagem , Antro Pilórico/patologia , Resultado do Tratamento
4.
Arq Gastroenterol ; 57(4): 507-510, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33331484

RESUMO

Therapeutic drug monitoring (TDM) of infliximab (IFX) has been recognized as an important strategy in the management of secondary loss of response to this agent, guiding clinical decision-making in the management of inflammatory bowel diseases (IBD). Although most of the data on the application of TDM for IFX refer to the maintenance phase of treatment, many studies have associated higher drug concentrations, specially in the induction phase, with achievement of important treatment targets, such as clinical remission and mucosal healing. This brief communication aims to summarize the literature on the use of TDM during induction phase of IFX and propose application of a simplified approach which can be useful into clinical practice, aiming better outcomes to IBD patients.


Assuntos
Monitoramento de Medicamentos , Doenças Inflamatórias Intestinais , Infliximab/uso terapêutico , Algoritmos , Fármacos Gastrointestinais/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico
5.
Acta Gastroenterol Belg ; 83(4): 657-659, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33321025

RESUMO

Discontinuation of treatment in children with inflammatory bowel disease (IBD) in long-term remission remains debatable. The risk of relapse is one of the main concerns in the consideration of reduction or cessation of treatment. In 2017 all paediatric IBD patients treated with originator infliximab at the Department of Paediatric Gastroenterology, Ghent University Hospital, were switched to biosimilar Remsima®. Faecal calprotectin, infliximab through levels and antibodies, white cell count, haemoglobin and C-reactive protein were measured before and after switching to biosimilar. In total 21 IBD patients (3 Ulcerative Colitis - 19 CD) between 7 and 15 years old were switched. Three (14%) patients with CD in clinical, biochemical and histological remission had an unmeasurable through level and antibodies for infliximab, after 22 to 82 months of use. Switching to another treatment or cessation was discussed with patients and parents, all 3 patients decided to stop treatment. All 3 are still in clinical remission 21 to 24 months after treatment stop. Six-monthly follow-up is foreseen.


Assuntos
Medicamentos Biossimilares , Doença de Crohn , Doenças Inflamatórias Intestinais , Adolescente , Medicamentos Biossimilares/uso terapêutico , Criança , Doença de Crohn/tratamento farmacológico , Substituição de Medicamentos , Fármacos Gastrointestinais/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento , Suspensão de Tratamento
6.
PLoS One ; 15(12): e0243729, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33315881

RESUMO

This study aimed to directly analyze the potential relationship of anti-nuclear antibodies (ANA) before and after the administration of TNF-α inhibitors (TNFi) with the appearance of anti-drug antibodies (ADrA) in patients with rheumatoid arthritis (RA). A total of 121 cases, viz., 38, 53, and 30 cases treated with infliximab (IFX), adalimumab (ADA), and etanercept (ETN), respectively, were enrolled. The ANA titers were measured using indirect immunefluorescence assay (IF-ANA) and multiplex flow immunoassay (ANA Screen) before and serially during the therapy. The anti-IFX antibodies (HACA) and anti-ADA antibodies (AAA) were measured with a radioimmunoassay. ADrA turned positive in 14 (36.8%) among 38 patients treated with IFX, and 16 (30.2%) among 53 treated with ADA. All of them were positive for IF-ANA before TNFi administration, while ADrA never appeared in any of the 15 patients negative for IF-ANA (< 40). IF-ANA of high titers (≥ 320 and ≥ 640) before IFX treatment showed a significant association with the appearance of HACA 52 weeks after IFX (P = 0.040 and 0.017, respectively), whereas AAA appearance was not related to IF-ANA titers before treatment. Moreover, IF-ANA of high titers before IFX treatment was significantly associated with inefficacy and discontinuation of the treatment. The positivity of anti-SS-A antibodies before therapy might be a risk factor for ADrA appearance in patients treated with IFX or ADA. The percentage of patients whose IF-ANA titers increased was significantly higher with IFX than with ADA or ETN treatments (P = 0.026 and 0.022, respectively). High ANA titers and positive ANA Screen after IFX therapy showed a significant association with HACA appearance and possibly led to treatment failure. Among the three TNFi, only IFX showed a close relationship with IF-ANA and ADrA appearance, suggesting the interaction of immunogenicity with autoimmunity as well as the advantage of ANA measurement before TNFi therapy.


Assuntos
Adalimumab/imunologia , Anticorpos/imunologia , Antirreumáticos/imunologia , Artrite Reumatoide/tratamento farmacológico , Etanercepte/imunologia , Infliximab/imunologia , Adalimumab/uso terapêutico , Adulto , Idoso , Anticorpos Antinucleares/imunologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/imunologia , Etanercepte/uso terapêutico , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/antagonistas & inibidores
7.
Zhonghua Yi Xue Za Zhi ; 100(42): 3303-3308, 2020 Nov 17.
Artigo em Chinês | MEDLINE | ID: mdl-33202491

RESUMO

Objective: To explore the associations of regulatory B cells (Breg cells) and regulatory T cells (Treg cells) with the clinical effect of Infliximab in the treatment of Chinese patients with Crohn's disease (CD). Methods: From January 2017 to June 2019, a total of 32 CD patients at active stage and 33 age and gender-matched healthy controls were collected from the Second Affiliated Hospital of Wenzhou Medical University in this study. Approximate 5 ml of peripheral fasting venous blood was obtained from every subject. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood. Then multi-color flow cytometry was applied to determine the proportion of Breg (CD3-CD19+IL-10+B cells) in B cells and the proportion of Treg (CD4+CD25+Foxp3+T cells) in CD4+T cells. Infliximab (5 mg/kg) was given intravenously at week 0, 2 and 6 to induce CD remission, and then maintained with the same dose of Infliximab every 8 weeks. And the proportions of Breg and Treg were examined at week 14 of Infliximab treatment, then compared with those of week 0. Simultaneously, C-reactive protein (CRP), leucocyte count, platelet count, erythrocyte sedimentation rate were detected in CD patients to assess the clinical effect at week 0 and 14 of Infliximab treatment. Results: Before infliximab treatment, compared with healthy controls, the proportion of Breg in B cells was significantly increased [(3.15±1.17)% vs (2.64±0.38)%, P=0.024)], and the proportion of Treg in CD4+T cells was significantly decreased [(2.15±0.49)% vs (4.25±0.41)%, P<0.001] in CD patients. And the proportion of Breg was positively related with the proportion of Treg in CD patients either at week 0 or week 14 of Infliximab treatment (r=0.628, P<0.001; r=0.749, P<0.001). At week 14 of Infliximab treatment, according to symptoms, Crohn's disease activity index (CDAI) and endoscopic mucosal healing, CD patients were classified as remission group (CDAI<150 and endoscopic mucosal healing, R group) and non-remission group (CDAI≥150 or mucosal non-healing group, N group). Compared with CD patients at week 0 of Infliximab treatment, both the proportion of Breg and Treg were significantly enhanced [(5.89±2.60)% vs (3.19±1.27)%, P<0.001; (4.59±0.72)% vs (2.08±0.47)%, P<0.001], whereas CDAI and CRP was significantly reduced [CDAI: (63.19±14.69) vs (195.62±58.13), P<0.001; CRP: (3.65±2.23) mg/L vs (29.80±30.06) mg/L, P<0.001] in R group at week 14 of Infliximab treatment. The proportions of Breg and Treg were negatively related with the CRP (r=-0.279, P=0.026; r=-0.406, P=0.001) and CDAI (r=-0.409, P=0.001; r=-0.708, P<0.001) in CD patients at week 0 and 14 of Infliximab treatment. At week 14 of Infliximab treatment, ROC curve analysis showed that the predictive value of "Breg+Treg" for the effect of Infliximab was higher than the other parameters (area under ROC: 0.782, cutoff value: 0.895 5, P=0.034). Conclusions: Breg cells and Treg cells are not only significantly correlated with CD disease activity, but the combined detection of the two types of immune cells has higher clinical value for predicting the effect of Infliximab in CD patients at active stage.


Assuntos
Linfócitos B Reguladores , Doença de Crohn , Proteína C-Reativa , Doença de Crohn/tratamento farmacológico , Humanos , Infliximab/uso terapêutico , Linfócitos T Reguladores
8.
Medicine (Baltimore) ; 99(44): e22897, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126343

RESUMO

Inflammatory bowel disease (IBD) in Asia has become increasingly prevalent. As a treatment of IBD, many immunomodulators and biological agents were introduced and shown to be effective in inducing and maintaining remission. However, many cases with treatment failure were reported. To overcome the failure, combination therapy of immunomodulatory and biologics have emerged, showing better outcomes by optimizing biologic pharmacokinetics and minimizing immunogenicity. Adversely, rates of tuberculosis (TB) have been increased as a result. The aim of this study is to compare the risk of TB according to the therapy using large population data.We used data from the South Korean Health Insurance and Review Agency over the period 2008-2016 and calculated the hazard ratio (HR) for TB in IBD. We compared the risk of TB according to the medication: infliximab only, azathioprine only (AZA), combination of azathioprine and infliximab (CAI), azathioprine monotherapy and infliximab monotherapy (AIM), and azathioprine and infliximab whether simultaneously or separately (AISS).In IBD patients, a total of 249 patients were identified as active TB. After one-to-one matching with age, sex and disease duration, the risks of TB were significantly higher in AZA group (HR, 2.06; 95% CI, 1.35-3.12, P < .001), AIM group (HR, 3.26; 95% CI, 1.18-9.05, P = .02), AISS group (HR, 3.50; 95% CI, 1.92-6.37, P < .001), and CAI group (HR, 5.67; 95% CI, 2.42-10.21, P < .001), and the HR increased gradually in this order. In UC patients, the results were in similar pattern, but this pattern was not observed in CD patients in our study.Our study shows that Korean IBD patients are at risk of TB, and the risk increases with usage of IBD medication; moreover, the risk is the highest if combination therapy is used. These results highlight the importance of screening for TB in IBD patients, especially in combination therapy.


Assuntos
Azatioprina/uso terapêutico , Quimioterapia Combinada/métodos , Infliximab/uso terapêutico , Tuberculose , Imunidade Adaptativa/efeitos dos fármacos , Produtos Biológicos/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/imunologia , Quimioterapia de Manutenção/efeitos adversos , Quimioterapia de Manutenção/métodos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Medição de Risco , Fatores de Risco , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/prevenção & controle
11.
Int J Hematol ; 112(6): 841-850, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32875487

RESUMO

Many drugs are used for unapproved indications in Japan for post hematopoietic stem cell transplant (HCT) complications. To investigate unapproved or off-label drug usage for graft-versus-host disease (GVHD) and virus infections after allogeneic HCT, we analyzed the data of Japanese HCT registry. Between 2006 and 2017, 39,941 adults and children received HCT for a variety of disease and their transplant data were captured in the registry. Among them, 14,687 and 8914 patients receiving treatment for acute and/or chronic GVHD, 24,828 patients with cytomegalovirus (CMV) infection or receiving therapies for CMV, and 4943 who received treatment for other viral infections were included in the analyses of off-label or unapproved drugs. For GVHD, mycophenolate mofetil was the most frequently used off-label drug, followed by beclomethasone, infliximab, and etanercept. For viral infections other than CMV, foscarnet was the most frequently used off-label drug. Cidofovir, which is not approved for use in Japan, was mainly used for adenovirus infection. This study demonstrated that numerous off-label and unapproved drugs have been used as key drugs for GVHD and post-transplant viral infection, and the real world date in the transplant registry may serve as an important asset to regulatory purposes.


Assuntos
Beclometasona/uso terapêutico , Cidofovir/uso terapêutico , Etanercepte/uso terapêutico , Foscarnet/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infliximab/uso terapêutico , Ácido Micofenólico/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Sistema de Registros , Viroses/tratamento farmacológico , Viroses/etiologia , Doença Aguda , Adulto , Doença Crônica , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/etiologia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Uso Off-Label , Transplante Homólogo
12.
Croat Med J ; 61(4): 333-337, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32881431

RESUMO

AIM: To assess C-reactive protein to albumin ratio (CAR) before and after treatment with biological agents in patients with psoriasis to determine whether CAR can be used as an inflammation biomarker. METHODS: Medical records of patients with psoriasis treated with biological agents at the Department of Dermatology, Gazi University Hospital were retrospectively evaluated between June 2018 and August 2019. The patients were divided into four groups based on the type of treatment (adalimumab, ustekinumab, infliximab, secukinumab). CAR was evaluated before and three months after treatment. RESULTS: The study enrolled 157 patients with psoriasis vulgaris (91 male) aged between 18 and 85. CAR significantly decreased in all treatment groups (adalimumab group P<0.001; ustekinumab P=0.006; infliximab P=0.007; secukinumab P<0.001). The most prominent decrease in CAR was observed in patients treated with secukinumab (median CAR before treatment 1.52 [1.01-3.04] and after treatment 0.84 [0.62-0.99]). CONCLUSION: CAR may be a good indicator of systemic inflammation in psoriasis patients treated with biological agents.


Assuntos
Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Fármacos Dermatológicos/uso terapêutico , Inflamação/sangue , Psoríase/tratamento farmacológico , Albumina Sérica/metabolismo , Adalimumab/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Psoríase/sangue , Estudos Retrospectivos , Resultado do Tratamento , Ustekinumab/uso terapêutico , Adulto Jovem
13.
Medicine (Baltimore) ; 99(31): e21447, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756163

RESUMO

BACKGROUND: The comparative efficacy and safety of small molecule and biological agents in the treatment of psoriatic arthritis (PsA) remain unknown. OBJECTIVES: To compare the efficacy and safety of 14 small molecule and biological agents by network meta-analysis (NMA). METHODS: Relevant randomized controlled trials involving biological treatments for PsA were identified by searching PubMed, Cochrane Library, EMBASE, Web of Science, and Clinicaltrials.gov and by manual retrieval, up to June 2018. NMA was conducted with Stata 14.0 based on the frequentist method. Effect measures were odds ratios (ORs) with 95% confidence intervals (CIs). Intervention efficacy and safety were ranked according to the surface under the cumulative ranking curve (SUCRA). RESULTS: A total of 30 studies involving 10,191 adult subjects were included. According to NMA, ≥ 20% improvement in modifed American College of Rheumatology response criteria (ACR20) response, Psoriasis Area and Severity Index 75 (PASI75) response, and serious adverse events rate (SAEs) were observed. In direct comparisons, most of the biologics performed better than placebo in terms of ACR20 response rate and PASI75 response rate. Additionally, all medicines were comparable to placebo in terms of SAEs except secukinumab. In terms of mixed comparisons, with regard to the ACR20 response, etanercept (ETN) and infliximab (IFX) were more effective than golimumab (GOL), with ORs of 3.33 (95% CI: 1.17-9.48) and 1.24 (95% CI: 0.61-2.52), respectively. For PASI75 response, IFX was superior to certolizumab pegol (OR = 10.08, 95% CI: 1.54-75.48). In addition, these medicines were comparable to each other in terms of SAEs. ETN and IFX were shown to have the most favorable SUCRA for achieving improved ACR20 and PASI75 responses, respectively, while ABT-122 exhibited the best safety according to the SUCRA for SAEs. Considering both the efficacy (ACR20, PASI75) and safety (SAEs), GOL, ETN, and IFX are the top 3 treatments. CONCLUSIONS AND IMPLICATIONS: Direct and indirect comparisons and integrated results suggested that the 3 anti- tumor necrosis factor -α biologics (GOL, ETN, and IFX) can be considered the best treatments for PsA after comprehensive consideration of efficacy and safety.


Assuntos
Artrite Psoriásica/tratamento farmacológico , Fatores Biológicos/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Fatores Biológicos/efeitos adversos , Estudos de Casos e Controles , Certolizumab Pegol/uso terapêutico , Etanercepte/uso terapêutico , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metanálise em Rede , Placebos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Índice de Gravidade de Doença , Resultado do Tratamento
14.
Medicine (Baltimore) ; 99(30): e21151, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791688

RESUMO

BACKGROUND: The introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) into clinical practice has dramatically improve the clinical outcomes of individuals with rheumatoid arthritis (RA). However, bDMARDs are associated with high costs, which has resulted in restricted treatment access and a burden on medical insurance finances. Although biosimilars offer cost-saving, their effectiveness and safety must be established in Post-Marketing Surveillance (PMS). Infliximab (IFX), a chimeric monoclonal antibody to TNF-alpha, is the first bDMARD; its biosimilar, CT-P13, is the first biosimilar DMARD approved for RA treatment in Japan. We will evaluate whether switching from originator IFX to CT-P13 is not inferior for maintaining non-clinical relapse to continued treatment with originator IFX in RA patients achieving clinical remission. METHODS/DESIGN: This study is an interventional, multicenter, open-label, single-arm against historical control and noninferiority clinical trial with a 24-week follow-up. Eighty RA patients who are treated by originator IFX for ≥24 weeks and are achieving clinical remission will be included. Patients will be switched to CT-P13 with the unchanged dosing regimen. We will evaluate disease activity by measuring clinical disease activity indices and by using musculoskeletal ultrasound (MSUS). The primary endpoint is the ratio of patients who experience a nonclinical relapse during the study period. Important secondary endpoints are the changes from the baseline of the MSUS scores. We will also comprehensively analyze the serum levels of many biomarkers such as cytokines and chemokines. DISCUSSION: The study results are expected to show the noninferiority of switching to CT-P13 over the continuation of originator IFX. The strength of this study is its prospective evaluation of therapeutic efficacy using not only clinical disease activity indices but also MSUS to accurately and objectively evaluate disease activity at the joint level among patients drawn from multiple centers with a standardized evaluation by MSUS. We will explore whether parameters at baseline can predict a nonclinical relapse after switching from originator IFX to CT-P13 by integrating multilateral assessments, i.e., clinical disease activity indices, MSUS findings, and serum biomarkers. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp) on October 11, 2019 as jRCTs071190030.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Medicamentos Biossimilares/uso terapêutico , Quimiocinas/sangue , Infliximab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico por imagem , Biomarcadores/sangue , Substituição de Medicamentos , Estudos de Equivalência como Asunto , Humanos , Japão , Quimioterapia de Manutenção , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Índice de Gravidade de Doença , Ultrassonografia , Adulto Jovem
15.
Brasília; CONITEC; ago. 2020. ilus, tab.
Não convencional em Português | BRISA/RedTESA | ID: biblio-1122923

RESUMO

INTRODUÇÃO: A artrite psoriaca (AP) e a doenca articular inflamatoria associada a psoriase, tambem autoimune, poligenica, de etiologia indefinida, na qual as citocinas relacionadas aos linfocitos T tem um papel central como na psoriase. Estima-se que a prevalencia geral da AP esteja em torno de 0,02% a 0,25% e que 1 em cada 4 pacientes com psoriase tem artrite psoriaca: 23,8% (IC 95%: 20,1% a 27,6%). No Sistema Unico de Saude (SUS) e garantido aos pacientes o acesso as opcoes de tratamentos com medicamentos, incluindo os antiinflamatorios nao esteroidais (AINE) ibuprofeno e naproxeno; os glicocorticoides prednisona e metilprednisolona; os medicamentos modificadores do curso da doenca sinteticos (MMCD-s) sulfassalazina (SSZ), metotrexato (MTX), leflunomida e ciclosporina; os MMCD biológicos (MMCD-b) adalimumabe, etanercepte, infliximabe e golimumabe; e o inibidor de citocinas anti-IL-17 secuquinumabe. PERGUNTA: O uso de ixequizumabe e eficaz, seguro e custo-efetivo para o tratamento de pacientes adultos com AP ativa, com uma resposta insuficiente ou intolerantes ao tratamento com um MMCD biologico? TECNOLOGIA: Ixequizumabe (TaltzR). EVIDÊNCIAS CIENTÍFICAS: Uma revisao sistematica com meta-analise em rede objetivou avaliar a eficacia e seguranca comparativa dos biologicos pertencentes a classe dos inibidores da interleucina (IL-6, IL-12/23 e IL-17) em pacientes com artrite psoriaca ativa. Foi avaliado o desempenho das tecnologias quanto as respostas no instrumento ACR (ACR20, ACR50), na semana 24; qualquer evento adverso (EA); eventos adversos graves (EAG); e tolerabilidade (descontinuacao devido a EA), na semana 16 ou 24. Apos recuperar 329 estudos, a revisão incluiu 6 estudos avaliando os inibidores de interleucina secuquinumabe, ustequinumabe, clazaquizumabe e ixequizumabe, com um total de 2.411 pacientes. Na analise de risco de vies, nao foram identificados pontos criticos, exceto o fato de que todos os seis estudos relataram o uso da ultima observacao transportada para imputacao de dados ausentes (Do ingles, last observation carried forward - LOCF) e que todos os estudos incluidos receberam financiamento de um organismo comercial com fins lucrativos. Ao realizar o ranqueamento com todos os tratamentos disponiveis no SUS (nao apenas os medicamentos em discussao neste relatorio), com base nas estimativas de SUCRA, os resultados do estudo indicam que o secuquinumabe 300 mg mensalmente tem a maior efetividade na obtencao de respostas ACR20 (SUCRA = 96,42) e ACR50 (SUCRA = 91,64). O estudo tambem indica que clazaquizumabe 200mg mensalmente, ustequinumabe 45mg a cada 12 semanas e secuquinumabe 150mg mensalmente tenham a menor probabilidade de ter EA, EAG e descontinuacao devido a EA. Na relacao geral do desempenho dos tratamentos em todos os desfechos de efetividade e seguranca, o secuquinumabe se destaca como a melhor opcao de tratamento em ambas as doses de 300 mg e 150 mg e o ixequizumabe a pior opcao para o tratamento da artrite psoriaca. Apos a condução de uma atualizacao da meta-analise em rede para incluir dois novos estudos do ixequizumabe (SPIRIT-P2 e SPIRIT-H2H), nao considerados na meta-analise original, pode-se observar que o secuquinumabe ainda se mantem com maior probabilidade no ranking de melhor tratamento. Em ambos os desfechos de efetividade e seguranca, o nivel de certeza das evidencias foi considerado moderado, com reducoes de efetividade devido a limitada similaridade das populacoes estudadas com ixequizumabe, secuquinumabe, a linha de tratamento em discussão (falha aos anti-TNF) e reducoes devido a imprecisao no desfecho de EAG. AVALIAÇÃO ECONÔMICA: Para a analise economica, o demandante encaminhou um estudo de "analise de custo por resposta" ou "custo por respondedor", que foi atualizado incluindo a comparacao com o secuquinumabe. Nessa linha, ao considerar os custos e benefícios incrementais em relacao ao adalimumabe, seriam necessarios R$ 19.350,54 para cada resposta adicional no ACR50 com o secuquinumabe. O medicamento ixequizumabe nao demonstrou superioridade na obtencao do ACR50 quando comparado ao adalimumabe, mas sim no desfecho combinado do ACR50/PASI100, onde seriam necessarios R$ 71.284,24 por cada resposta adicional no ACR50/PASI100. Ressalta-se que tal analise carece do rigor metodologico das avaliacoes economicas completas e seus resultados possuem serias limitacoes de interpretacao. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: O demandante encaminhou um modelo de impacto orcamentario com o objetivo de analisar o impacto da incorporacao de ixequizumabe ao longo de 5 anos no tratamento de pacientes com artrite psoriaca na perspectiva do SUS. Apos a analise critica do modelo encaminhado, considerou-se possuir um racional adequado e coerente com a perspectiva do SUS, contudo, com pontos criticos a serem revisados. Em sua proposta original, o demandante apresenta uma estimativa de economia de R$ 5,6 milhoes em cinco anos. Com a revisao e atualizacao dos dados, sobretudo ao considerar os custos do tratamento de inducao, essa economia deixa de existir e passa a ser estimado um impacto incremental de mais de R$ 58 milhoes. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Foram detectadas no horizonte seis potenciais tecnologias para o tratamento de pacientes com artrite psoriaca com uma resposta insuficiente ou intolerantes ao tratamento com um ou mais MMCD: apremilaste, bimequizumabe, filgotinibe, guselcumabe, risanquizumabe, upadacitinibe. CONSIDERAÇÕES: A partir das estimativas de efetividade comparativa disponiveis, por meio de meta-analises em rede, e possivel observar que o secuquinumabe, tratamento disponivel no SUS, se destaca como a melhor opcao de tratamento na indicacao dessa submissao quando comparado a outras opcoes, inclusive o ixequizumabe, que foi considerada a pior opcao para o tratamento da artrite psoriaca na relacao geral do desempenho nos desfechos de efetividade e seguranca. Alem disso, estima-se que a incorporacao do ixequizumabe possa implicar um impacto incremental de mais de R$ 58 milhoes. RECOMENDAÇÃO PRELIMINAR DA CONITEC: A Conitec, em sua 85a reuniao ordinaria, no dia 04 de fevereiro de 2020, recomendou a nao incorporacao no SUS do ixequizumabe para artrite psoriaca ativa com resposta insuficiente ou intolerante ao tratamento com medicamentos modificadores do curso da doenca. CONSULTA PÚBLICA: Foram recebidas 134 contribuicoes tecnico-cientificas e 222 contribuicoes de experiencia ou opiniao, sendo a maioria discordante da recomendacao preliminar da Conitec. Apos analise do texto das contribuicoes, foram identificados pontos como o anseio por novas opcoes terapeuticas, dificuldade de acesso pelo alto custo unitario do medicamento, assim como foram apresentados novos dados tecnicos e ressaltadas limitacoes da analise preliminar. No entanto, nao foram fornecidas evidencias cientificas que dessem suporte a superioridade do ixequizumabe frente ao secuquinumabe ou que fornecessem melhores subsidios de comparacao do que o uso da comparacao indireta. O laboratorio fabricante ofereceu uma nova proposta de preco equivalente a reducao de 2,7% do preco proposto inicialmente e um novo modelo de impacto orcamentario indicando uma reducao de gastos de ate R$ 49.893.362,00 ao longo dos 5 anos na ocasiao de incorporacao na mesma linha e indicacao do secuquinumabe. A Conitec entendeu que nao houve argumentacao suficiente para alterar sua recomendação inicial, pela nao incorporacao do ixequizumabe, devido a incerteza de beneficios em relacao ao perfil de desempenho de efetividade e seguranca das opcoes terapeuticas ja disponiveis no SUS. RECOMENDAÇÃO FINAL: Os membros da Conitec presentes na 89a reuniao ordinaria no dia 06 de agosto de 2020, deliberaram, por unanimidade, por recomendar a nao incorporacao no SUS do ixequizumabe para artrite psoriaca ativa com resposta insuficiente ou intolerante ao tratamento com medicamentos modificadores do curso da doenca. Considerou-se os mesmos argumentos para a recomendacao preliminar, o ixequizumabe nao apresenta beneficios em relacao ao perfil de desempenho de efetividade e seguranca das opcoes terapeuticas ja disponiveis no SUS. DECISÃO: Nao incorporar o ixequizumabe para tratamento de pacientes adultos com artrite psoriaca ativa com resposta insuficiente ou intolerante ao tratamento com um ou mais medicamentos modificadores do curso da doenca, no ambito do Sistema Unico de Saude - SUS, conforme Portaria no 31, publicada no Diario Oficial da Uniao no 160, secao 1, pagina 118, em 20 de agosto de 2020.


Assuntos
Humanos , Artrite Psoriásica/tratamento farmacológico , Interleucinas/uso terapêutico , Adalimumab/uso terapêutico , Infliximab/uso terapêutico , Etanercepte/uso terapêutico , Avaliação da Tecnologia Biomédica , Sistema Único de Saúde , Brasil , Análise Custo-Benefício/economia
16.
Aliment Pharmacol Ther ; 52(4): 669-681, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32656800

RESUMO

BACKGROUND: Direct comparisons are lacking between vedolizumab and tumour necrosis factor (TNF)-antagonist therapy in Crohn's disease (CD). AIM: To compare safety and effectiveness of vedolizumab and TNF-antagonist therapy in adult CD patients. METHODS: Retrospective observational cohort (May 2014-December 2017) propensity score-weighted comparison of vedolizumab vs TNF-antagonist therapy (infliximab, adalimumab, certolizumab) in CD. Propensity scores were weighted for age, prior treatments, disease complications, extent and severity, steroid dependence, and concomitant immunosuppressive drug use. The primary outcome was comparative risk for infections or non-infectious serious adverse events (requiring antibiotics, antivirals, antifungals, hospitalisation, or treatment discontinuation, or resulting in death). Secondary comparative effectiveness outcomes were clinical remission (resolution of CD-related symptoms), steroid-free clinical remission and endoscopic remission (absence of ulcers/erosions). RESULTS: We included 1266 patients (n = 659 vedolizumab). Rates of non-infectious serious adverse events (odds ratio [OR] 0.072, 95% confidence interval [CI] 0.012-0.242), but not serious infections (OR 1.183, 95% CI 0.786-1.795), were significantly lower with vedolizumab vs TNF-antagonist therapy. Safety comparisons for non-infectious serious adverse events remained significant after adjusting for differences in duration of exposure. No significant difference was observed between vedolizumab and TNF-antagonist therapy for clinical remission (hazard ratio [HR] 0.932, 95% CI 0.707-1.228), steroid-free clinical remission (HR 1.250, 95% CI 0.677-2.310) or endoscopic remission (HR 0.827, 95% CI 0.595-1.151). TNF-antagonist therapy was associated with higher treatment persistence compared with vedolizumab. CONCLUSIONS: There was a lower risk of non-infectious serious adverse events, but not serious infections, with vedolizumab vs TNF-antagonist therapy, with no significant difference for achieving disease remission.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Doença de Crohn/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab/uso terapêutico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Certolizumab Pegol/uso terapêutico , Estudos de Coortes , Doença de Crohn/epidemiologia , Feminino , Humanos , Infliximab/uso terapêutico , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Adulto Jovem
17.
Medicine (Baltimore) ; 99(28): e20966, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664100

RESUMO

To investigate the effectiveness of dual filtration plasmapheresis (DFPP), a novel blood purification treatment, as a rapid and sustained disease-modifying therapy for active refractory rheumatoid arthritis (RA).A retrospective cohort study had been conducted. One hundred fifty three patients aged 18 years or older with active refractory RA were treated with DFPP combined with infliximab (IFX), IFX, or glucocorticoid (GC), all the above treatments were combined with methotrexate (MTX).Baseline characteristic of the 153 patients (DFPP: n = 53; IFX: n = 51; GC: n = 49) were similar across groups. The remission rate of CDAI (SDAI) in the DFPP treatment group was significantly higher than that of the IFX and GC group after 3 months of treatment. The remission rate of DFPP treatment group was above 50%, while in IFX and GC group, the rate of CDAI (SDAI) remission was 41.2% (37.3%) and 22.4% (14.2%) after 3 months of treatment.A combination of DFPP and biological agents can quickly induce remission or low disease activity of active refractory RA.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/terapia , Infliximab/uso terapêutico , Metotrexato/uso terapêutico , Plasmaferese/métodos , Adulto , Idoso , Estudos de Coortes , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
18.
Zhonghua Er Ke Za Zhi ; 58(7): 570-575, 2020 Jul 02.
Artigo em Chinês | MEDLINE | ID: mdl-32605341

RESUMO

Objective: To analyze the clinical characteristics and efficacy of drug treatment in children with inflammatory bowel disease (IBD) at different ages of onset. Methods: The clinical data of 87 children with IBD admitted to Department of Gastroenterology in Children's Hospital, Capital Institute of Pediatrics from January 2009 to December 2018 were collected. The patients were divided into four groups according to the age of onset: 0 -<2 years old group (36 cases), 2 -<6 years old group (10 cases), 6 -<10 years old group (12 cases) and 10 -<18 years old group (29 cases). The clinical manifestations, laboratory examination, endoscopic findings, pathologic and genetic changes, and treatment were compared among different age groups with chi-square test or Fisher's exact text. Results: (1) A total of 87 patients were diagnosed with IBD, including 50 Crohn's disease (CD) (57%), 25 ulcerative colitis (UC) (29%) and 12 unclassified inflammatory bowel disease (IBD-U) (14%). (2) Patients with fever accounted for 78% (28/36) and 8/10 in the 0 -<2 years old group and 2 -<6 years old group, respectively. Patients with abdominal pain and perianal diseases accounted for 6% (2/36) and 47% (17/36) in the 0 -<2 years old group, and their proportions were significantly different among the four groups (χ(2)=8.369, 40.317 and 13.130, all P<0.05). (3) Leukocytosis, thrombocytosis and anemia were more common in the 0-<2 years old group, seen in 72% (26/36), 31% (11/36) and 81% (29/36), respectively. There were significant differences in the changes of complete blood count among the four groups (χ(2)=21.919, 8.095 and 11.520, all P<0.05). (4) Colonic involvement accounted for 85% (17/20) in the 0 -<2 years old CD patients. While in the CD patients over 6 years old, 61% (14/23) had inflammation of ileum and colon, with a significant difference compared to that in patients under 6 years old (19% (5/27) , χ(2)=9.455, P=0.003). Also, the location of bowel inflammation among the four groups were significantly different (χ(2)=21.120, P<0.01). (5) Noncaseating granulomas were found in 15 (30%) CD patients, and crypt abscess was found in 11 (44%) UC patients. (6) Among the 24 patients whose genes were analyzed by high throughput sequencing, 12 had pathogenic single gene mutation. (7) There were 25 patients treated with total enteral nutrition. Among the 25 patients treated with thalidomide, 20 (80%) had clinical remission or partial remission. Among the 19 CD patients treated with infliximab (IFX), 14 had clinical remission at the 6(th) week of treatment, and the proportion of remission maintenance at the 30(th) week of treatment was 12/14. (8) The rate of clinical remission or partial remission was 64% (23/36) in the 0 -<2 years old group, 8/10 in the 2 -<6 years old group, 11/12 in the 6 -<10 years old group, and 83% (24/29) in the 10 -<18 years old group. Conclusions: The proportion of CD was higher than that of UC in this study. Infant onset inflammatory bowel disease was more likely to present with perianal lesions, and was usually associated with leukocytosis, thrombocytosis and anemia, and has high possibility of single gene mutation. IFX may be effective in treating CD.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Adolescente , Criança , Pré-Escolar , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Doença de Crohn/tratamento farmacológico , Nutrição Enteral , Fármacos Gastrointestinais/uso terapêutico , Humanos , Lactente , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Infliximab/uso terapêutico , Talidomida/uso terapêutico
19.
BMC Infect Dis ; 20(1): 464, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32615992

RESUMO

BACKGROUND: Despite successful clinical outcomes of biologic medications in patients with chronic rheumatic diseases, some considerable adverse effects such as infections remain a major concern. Possibility of tuberculosis (TB) reactivation over treatment with anti-tumor necrotizing factor (TNF) alpha agents has necessitated a screening test before initiation of treatment. However, screening over the course of treatment is not recommended in those patients with negative baseline screening tests. This study aimed to evaluate the efficacy of tuberculin skin test (TST) before treatment in patients with chronic rheumatologic diseases who were indicated to receive anti-TNF-alpha therapy and the necessity of repeating this test over the course of treatment. METHODS: In this prospective study, patients with chronic rheumatologic diseases receiving anti-TNF-alpha agents were studied in a two-year period. TST was performed before treatment and those with positive results were excluded from the study. Thereafter, treatment with anti-TNF-alpha agents was initiated with the indicated dose. TST was repeated before administration of biologic treatment until TST became positive or 16 weeks after the initiation of treatment with anti-TNF-alpha. RESULTS: A total of 51 cases were studied, of whom one patient (1.9%) was excluded due to positive TST before treatment. All participants received infliximab and the TST test became positive in one patient (2%) 2 weeks after receiving the first dose. Also, the results of further tests at weeks 6, 10, and 14 were all negative for the remaining patients. CONCLUSION: Due to the possibility of TST conversion after administration of anti-TNF-alpha therapy, it is important to consider TB monitoring in patients under treatment with these agents using available methods such as TST.


Assuntos
Antirreumáticos/uso terapêutico , Infliximab/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , Teste Tuberculínico/métodos , Tuberculose/diagnóstico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Antirreumáticos/farmacologia , Doença Crônica , Feminino , Humanos , Infliximab/farmacologia , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
20.
Lancet Gastroenterol Hepatol ; 5(10): 900-907, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32619413

RESUMO

BACKGROUND: The LIR!C trial showed that laparoscopic ileocaecal resection is a cost-effective treatment that has similar quality-of-life outcomes to treatment with infliximab, an anti-tumour necrosis factor (TNF) drug. We aimed to compare long-term outcomes of both interventions and identify baseline factors associated with the duration of treatment effect in each group. METHODS: In this retrospective follow-up study, we collected data from patients who participated in the LIR!C trial, a multicentre randomised controlled trial that compared quality of life after surgical resection versus infliximab in adult patients with non-stricturing and immunomodulator-refractory ileocaecal Crohn's disease. From Jan 1 to May 1, 2018, we collected follow-up data from the time from enrolment in the LIR!C trial until the last visit at either the gastrointestinal surgeon or gastroenterologist. In this study, outcomes of interest were need for surgery or repeat surgery or anti-TNF therapy, duration of treatment effect, and identification of factors associated with the duration of treatment effect. Duration of treatment effect was defined as the time without need for additional Crohn's disease-related treatment (corticosteroids, immunomodulators, biologics, or surgery). FINDINGS: We collected long-term follow-up data for 134 (94%) of 143 patients included in the LIR!C trial, of whom 69 were in the resection group and 65 were in the infliximab group. Median follow-up was 63·5 months (IQR 39·0-94·5). In the resection group, 18 (26%) of 69 patients started anti-TNF therapy and none required a second resection. 29 (42%) patients in the resection group did not require additional Crohn's disease-related medication, although 14 (48%) of these patients were given prophylactic immunomodulator therapy. In the infliximab group, 31 (48%) of 65 patients had a Crohn's disease-related resection, and the remaining 34 patients maintained, switched, or escalated their anti-TNF therapy. Duration of treatment effect was similar in both groups, with a median time without additional Crohn's disease-related treatment of 33·0 months (95% CI 15·1-50·9) in the resection group and 34·0 months (0·0-69·3) in the infliximab group (log-rank p=0·52). In both groups, therapy with an immunomodulator, in addition to the allocated treatment, was associated with duration of treatment effect (hazard ratio for resection group 0·34 [95% CI 0·16-0·69] and for infliximab group 0·49 [0·26-0·93]). INTERPRETATION: These findings further support laparoscopic ileocaecal resection as a treatment option in patients with Crohn's disease with limited (affected segment ≤40 cm) and predominantly inflammatory terminal ileitis for whom conventional treatment is not successful. FUNDING: None.


Assuntos
Ceco/cirurgia , Doença de Crohn/terapia , Íleo/cirurgia , Laparoscopia/métodos , Corticosteroides/uso terapêutico , Adulto , Ceco/patologia , Análise Custo-Benefício/métodos , Doença de Crohn/etiologia , Feminino , Seguimentos , Fármacos Gastrointestinais/uso terapêutico , Humanos , Íleo/patologia , Fatores Imunológicos/uso terapêutico , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
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