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1.
Medicine (Baltimore) ; 100(6): e24731, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578618

RESUMO

ABSTRACT: Administering double doses of infliximab or shortening its dosing interval for patients with Crohn disease who experience a loss of response to treatment is an accepted treatment method; however, the effectiveness and appropriate timing of treatment intensification remain unclear. We examined the treatment outcomes of patients with Crohn disease receiving infliximab therapy intensification.Among 430 patients with Crohn disease who were seen at our related facilities from July 2002 to July 2018, 46 patients (30 men and 16 women) who were followed up for diminished infliximab effects for >1 year after therapy intensification were included in this study. The relationship between patient background and continuation of therapy intensification was retrospectively examined through a logistic regression analysis.Among the 46 patients, 67.4% (31 cases) continued therapy intensification for 12 months. The treatment discontinuation rate after 12 months (7.1% vs 43.8%, P = .015) and the C-reactive protein levels at the start of therapy intensification (P = .0050) were significantly lower in the group in which treatment was strengthened due to remaining endoscopic findings (n = 14) than that due to clinical symptoms (n = 32). There was no significant difference in the rates of treatment discontinuation after 12 months of treatment strengthening between patients receiving double doses (n = 34) and those with shortened dosing intervals (n = 12).Infliximab treatment discontinuation seems to be less likely to occur in patients with Crohn disease who are receiving infliximab treatment intensification based on endoscopic findings of exacerbations than in patients whose treatment is based on clinical symptoms.


Assuntos
Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/administração & dosagem , Infliximab/administração & dosagem , Adolescente , Adulto , Idoso , Doença de Crohn/diagnóstico , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Estudos Retrospectivos , Adulto Jovem
2.
Arch Iran Med ; 24(2): 139-143, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33636983

RESUMO

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) may lead to the cytokine storm syndrome which may cause acute respiratory failure syndrome and death. Our aim was to investigate the therapeutic effects of infliximab, intravenous gammaglobulin (IVIg) or combination therapy in patients with severe COVID-19 disease admitted to the intensive care unit (ICU). METHODS: In this observational research, we studied 104 intubated adult patients with severe COVID-19 infection (based on clinical symptoms, and radiographic or CT scan parameters) who were admitted to the ICU of a multispecialty hospital during March 2020 in Tehran, Iran. All cases received standard treatment regimens as local protocol (Oseltamivir + hydroxychloroquine + lopinavir/ritonavir or sofosbuvir or atazanavir ± ribavirin). The cases were grouped as controls (n = 43), infliximab (n = 27), IVIg (n = 23) and combination (n = 11). RESULTS: There was no significant difference between controls and treatment groups in terms of underlying diseases or the number of underlying diseases. The mean age (SD) of cases was 72.42 (16.06) in the control group, 64.52 (12.965) in IVIg, 63.40 (17.57) in infliximab and 64.00 (11.679) in combination therapy; (P = 0.047, 0.031 and 0.11, respectively). Also, 37% in the infliximab group, 26.1% in IVIg, 45.5% in combination therapy, and 62.8% in the control group expired (all P < 0.05). Hazard ratios were 0.31 in IVIg (95% CI: 0.12-0.76, P = 0.01), 0.30 in infliximab (95% CI: 0.13-0.67, P = 0.004), 0.39 in combination therapy (95% CI: 0.12-1.09, P = 0.071). CONCLUSION: According to the findings of this study, it seems that infliximab and IVIg, alone or together, in patients with severe COVID-19 disease can be considered an effective treatment.


Assuntos
/tratamento farmacológico , Imunoglobulinas Intravenosas/administração & dosagem , Infliximab/administração & dosagem , Pacientes Internados , Unidades de Terapia Intensiva , Pandemias , Adulto , Antirreumáticos/administração & dosagem , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
3.
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
5.
Clin Drug Investig ; 41(1): 77-88, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33341911

RESUMO

BACKGROUND AND OBJECTIVES: Intravenous immunoglobulin (IVIG) therapy for acute-stage Kawasaki disease (KD) is the first-line treatment for preventing the development of coronary artery aneurysms (CAA). Corticosteroids (prednisolone) and infliximab are often used in patients at a high risk of CAA or those with CAA at diagnosis; however, there are only a few reports of non-responders to corticosteroids as an adjuvant therapy or rescue alternative to IVIG. In this study, we compared the therapeutic effects of primary and secondary prednisolone with IVIG for KD. METHODS: We established the following three protocols: A was a secondary rescue prednisolone protocol; B was no prednisolone and second-line infliximab protocol, and C was the primary prednisolone protocol. The indication for prednisolone administration was based on the following: primary prednisolone administration, Kobayashi score; and secondary administration, Shizuoka score. RESULTS: Four hundred and sixty-nine patients were enrolled in the three protocols. A comparison between primary and secondary prednisolone and IVIG, as the first-line therapy revealed that the number of first non-responders in C group was 7 (8.3%), which was significantly lower than the 50 (20.9%) in A group. There was a significant difference in the first and second non-responders among the three groups, and the number of non-responders in A group was 6 (2.5%), which was significantly lower than the 13 (9.9%) in B group (p < 0.001, by Bonferroni test). The multivariate logistic regression analysis showed that IVIG non-responders among the protocol groups had an adjusted odds ratio of 6.47. Fifteen IVIG non-responders were administered infliximab as a second-line therapy, and of them, 9 (60%) showed therapy resistance. CAA occurred in 21 patients (4.6%). There was no significant difference among each protocol group. CONCLUSIONS: The number of IVIG non-responders in the group with prednisolone administration was lower than that in the group without prednisolone administration. Secondary rescue infliximab therapy for IVIG non-responders resulted in a lower defervescence effect than the secondary rescue IVIG with prednisolone administration. Further prospective randomized studies are needed to identify factors useful for preventing IVIG non-responders and determine the optimal rescue therapy for preventing CAA.


Assuntos
Imunoglobulinas Intravenosas/administração & dosagem , Infliximab/administração & dosagem , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Prednisolona/administração & dosagem , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Masculino , Estudos Prospectivos
6.
Rev Esp Enferm Dig ; 113(2): 154, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33371704

RESUMO

The objective of this study was to determine the adherence to biological treatment in inflammatory bowel disease (IBD) patients during the COVID-19 pandemic at Hospital Universitario La Paz, in Madrid. All patients from our IBD Unit were informed via e-mail, social networks and websites about the convenience of continuing with treatment. In addition, patients were contacted by telephone a few days before to remind them of their appointment and the importance of adherence.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Fármacos Gastrointestinais/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/administração & dosagem , Adesão à Medicação/estatística & dados numéricos , Terapia Biológica , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade
7.
Cochrane Database Syst Rev ; 9: CD008333, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32990324

RESUMO

BACKGROUND: Anti-neutrophilic cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) are a group of rare auto-inflammatory diseases that affects mainly small vessels. AAV includes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Anti-cytokine targeted therapy uses biological agents capable of specifically targeting and neutralising cytokine mediators of the inflammatory response. OBJECTIVES: To assess the benefits and harms of anti-cytokine targeted therapy for adults with AAV. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (2019, Issue 7), MEDLINE and Embase up to 16 August 2019. We also examined reference lists of articles, clinical trial registries, websites of regulatory agencies and contacted manufacturers. SELECTION CRITERIA: Randomised controlled trials (RCTs) or controlled clinical trials of targeted anti-cytokine therapy in adults (18 years or older) with AAV compared with placebo, standard therapy or another modality and anti-cytokine therapy of different type or dose. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included four RCTs with a total of 440 participants (mean age 48 to 56 years). We analysed the studies in three groups: 1) mepolizumab (300 mg; three separate injections every four weeks for 52 weeks) versus placebo in participants with relapsing or refractory EGPA; 2) belimumab (10 mg/kg on days 0, 14, 28 and every 28 days thereafter until 12 months after the last participant was randomised) or etanercept (25 mg twice a week) with standard therapy (median 25 months) versus placebo with standard therapy (median 19 months) in participants with GPA/MPA; and 3) infliximab (3 mg/kg on days 1 and 14, before the response assessment on day 42) versus rituximab (0.375g/m2 on days 1, 8, 15 and 22) in participants with refractory GPA for up to 12 months. None of the studies were assessed as low risk of bias in all domains: one study did not report randomisation or blinding methods clearly. Three studies were at high risk and one study was at unclear risk of bias for selective outcome reporting. One trial with 136 participants with relapsing or refractory EGPA compared mepolizumab with placebo during 52 weeks of follow-up and observed one death in the mepolizumab group (1/68, 1.5%) and none in the placebo group (0/68, 0%) (Peto odds ratio (OR) 7.39, 95% confidence interval (CI) 0.15 to 372.38; low-certainty evidence). Low-certainty evidence suggests that more participants in the mepolizumab group had ≥ 24 weeks of accrued remission over 52 weeks compared to placebo (27.9% versus 2.9%; risk ratio (RR) 9.5, 95% CI 2.30 to 39.21), and durable remission within the first 24 weeks sustained until week 52 (19.1% mepolizumab versus 1.5% placebo; RR 13.0, 95% CI 1.75 to 96.63; number needed to treat for an additional beneficial outcome (NNTB) 6, 95% Cl 4 to 13). Mepolizumab probably decreases risk of relapse (55.8% versus 82.4%; RR 0.68, 95% CI 0.53 to 0.86; NNTB 4, 95% CI 3 to 9; moderate-certainty evidence). There was low-certainty evidence regarding similar frequency of adverse events (AEs): total AEs (96.9% versus 94.1%; RR 1.03, 95% CI 0.96 to 1.11), serious AEs (17.7% versus 26.5%; RR 0.67, 95% CI 0.35 to 1.28) and withdrawals due to AEs (2.9% versus 1.5%; RR 2.00, 95% CI 0.19 to 21.54). Disease flares were not measured. Based on two trials with different follow-up periods (mean of 27 months for etanercept study; up to four years for belimumab study) including people with GPA (n = 263) and a small group of participants with MPA (n = 22) analysed together, we found low-certainty evidence suggesting that adding an active drug (etanercept or belimumab) to standard therapy does not increase or reduce mortality (3.4% versus 1.4%; Peto OR 2.45, 95% CI 0.55 to 10.97). Etanercept may have little or no effect on remission (92.3% versus 89.5%; RR 0.97, 95% CI 0.89 to 1.07), durable remission (70% versus 75.3%; RR 0.93, 95% CI 0.77 to 1.11; low-certainty evidence) and disease flares (56% versus 57.1%; RR 0.98, 95% CI 0.76 to 1.27; moderate-certainty evidence). Low-certainty evidence suggests that belimumab does not increase or reduce major relapse (1.9% versus 0%; RR 2.94, 95% CI 0.12 to 70.67) or any AE (92.5% versus 82.7%; RR 1.12, 95% CI 0.97 to 1.29). Low-certainty evidence suggests a similar frequency of serious or severe AEs (47.6% versus 47.6%; RR 1.00, 95% CI 0.80 to 1.27), but more frequent withdrawals due to AEs in the active drug group (11.2%) compared to the placebo group (4.2%), RR 2.66, 95% CI 1.07 to 6.59). One trial involving 17 participants with refractory GPA compared infliximab versus rituximab added to steroids and cytotoxic agents for 12 months. One participant died in each group (Peto OR 0.88, 95% CI, 0.05 to 15.51; 11% versus 12.5%). We have very low-certainty evidence for remission (22% versus 50%, RR 0.44, 95% Cl 0.11 to 1.81) and durable remission (11% versus 50%, RR 0.22, 95% CI 0.03 to 1.60), any severe AE (22.3% versus 12.5%; RR 1.78, 95% CI 0.2 to 16.1) and withdrawals due to AEs (0% versus 0%; RR 2.70, 95% CI 0.13 to 58.24). Disease flare/relapse and the frequency of any AE were not reported. AUTHORS' CONCLUSIONS: We found four studies but concerns about risk of bias and small sample sizes preclude firm conclusions. We found moderate-certainty evidence that in patients with relapsing or refractory EGPA, mepolizumab compared to placebo probably decreases disease relapse and low-certainty evidence that mepolizumab may increase the probability of accruing at least 24 weeks of disease remission. There were similar frequencies of total and serious AEs in both groups, but the study was too small to reliably assess these outcomes. Mepolizumab may result in little to no difference in mortality. However, there were very few events. In participants with GPA (and a small subgroup of participants with MPA), etanercept or belimumab may increase the probability of withdrawal due to AEs and may have little to no impact on serious AEs. Etanercept may have little or no impact on durable remission and probably does not reduce disease flare.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Imunossupressores/administração & dosagem , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/mortalidade , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Síndrome de Churg-Strauss/tratamento farmacológico , Etanercepte/administração & dosagem , Etanercepte/efeitos adversos , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Imunossupressores/efeitos adversos , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Poliangiite Microscópica/tratamento farmacológico , Pessoa de Meia-Idade , Números Necessários para Tratar , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Prevenção Secundária , Esteroides/administração & dosagem
9.
Medicine (Baltimore) ; 99(32): e21480, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769882

RESUMO

BACKGROUND: The introduction of biological disease-modifying anti-rheumatic drugs into clinical practice has dramatically improved the clinical outcomes of individuals with rheumatoid arthritis (RA). We are conducting the IFX-SIRIUS STUDY I that evaluates whether switching from originator infliximab (IFX) to its biosimilar, CT-P13, is not inferior in maintaining nonclinical relapse to continue treatment with originator IFX in patients with RA achieving clinical remission. It is the next great issue whether disease activity can be maintained in good condition after discontinuation of CT-P13 because no evidence is available regarding the clinical value of discontinuing biosimilars in patients with RA. Thus, we will evaluate whether a condition without clinical relapse will be maintained after discontinuation of CT-P13 in patients with RA, achieving clinical remission or low disease activity during the IFX-SIRIUS STUDY I. METHODS/DESIGN: This study is an interventional, multicenter, open-label, single-arm clinical trial with a 48-week follow-up. Patients with RA who are treated with CT-P13 and sustained nonclinical relapse during the IFX-SIRIUS STUDY I will be included. Patients will discontinue CT-P13 after the study period of the IFX-SIRIUS STUDY I. We will evaluate disease activity by clinical disease activity indices and musculoskeletal ultrasound (MSUS). The primary endpoint is the proportion of patients who do not have clinical 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 multiple biomarkers, such as cytokines and chemokines. In addition, if a clinical relapse occurs in patients after the discontinuation of CT-P13, we will evaluate the effectiveness and safety of restarting CT-P13. DISCUSSION: The study results are expected to show the clinical benefit of the discontinuation of CT-P13 and effectiveness and safety of restarting CT-P13 after clinical relapse. The strength of this study is to prospectively evaluate the therapeutic effectiveness by not only clinical disease activity indices but also standardized MSUS findings in multiple centers. We will explore whether parameters at baseline can predict a nonclinical relapse after the discontinuation of CT-P13 by integrating multilateral assessments, that is, patient's characteristics, 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 April 20, 2020 as jRCTs071200007.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Reumatoide/patologia , Medicamentos Biossimilares/administração & dosagem , Substituição de Medicamentos , Infliximab/administração & dosagem , Adulto , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Biomarcadores/análise , Estudos de Equivalência como Asunto , Feminino , Humanos , Quimioterapia de Indução , Japão , Masculino , Recidiva , Resultado do Tratamento , Ultrassonografia
10.
J Allergy Clin Immunol ; 146(4): 786-789, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32710973

Assuntos
Antivirais/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Síndrome da Liberação de Citocina/prevenção & controle , Hipersensibilidade a Drogas/etiologia , Fatores Imunológicos/efeitos adversos , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Corticosteroides/uso terapêutico , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/análogos & derivados , Amidas/administração & dosagem , Amidas/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antivirais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/administração & dosagem , Indóis/administração & dosagem , Indóis/efeitos adversos , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Índice de Gravidade de Doença
11.
Med. clín (Ed. impr.) ; 154(12): 475-480, jun. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-195673

RESUMO

INTRODUCCIÓN: CT-P13 es un fármaco biosimilar de infliximab (IFX), efectivo en pacientes con enfermedad inflamatoria intestinal (EII). La medición de niveles de IFX y anticuerpos anti-IFX forma parte del tratamiento integral de dicha enfermedad. OBJETIVO: Comparar la respuesta clínica en función de un abordaje estrictamente clínico (CLN) o proactivo (PRO) basado en la medición de niveles en la semana 14, en la práctica clínica. MÉTODOS: Estudio prospectivo en pacientes que inician CT-P13 por EII. En el grupo PRO se midieron sistemáticamente los niveles de IFX y de anticuerpos postinducción (semana 14) y se intensificaron aquellos con niveles infraterapéuticos (<3μg/ml), independientemente de la respuesta clínica. RESULTADOS: Se incluyeron 77 pacientes (23 colitis ulcerosa y 54 enfermedad de Crohn). Ambos grupos, PRO (n=41) y CLN (n=36) presentaron una eficacia inicial y a largo plazo sin diferencias significativas. En la semana 14 hubo un 61% de remisión clínica (RC) (58,5% PRO, 63,9% CLN) y un 80,5% de al menos respuesta parcial (RP) (80,5% PRO, 80,6% CLN). En la semana 54 hubo un 68,8% de RC (61% PRO, 77,8% CLN) y un 76,6% de al menos RP (73,2% PRO, 80,6% CLN). De los pacientes en RC en la semana 14 (24 PRO, 23 CLN), 13 del grupo PRO fueron intensificados por niveles infraterapéuticos. En este subgrupo no se observaron diferencias significativas en la pérdida de respuesta secundaria (PRO 0%, CLN 8,7%). CONCLUSIÓN: Un manejo proactivo no mejoró las tasas de respuesta ni la remisión en el primer año. La intensificación de pacientes en RC y niveles infraterapéuticos postinducción no parece prevenir de forma significativa la pérdida de respuesta secundaria en el primer año


INTRODUCTION: CT-P13 is a biosimilar drug of infliximab (IFX), effective in patients with inflammatory bowel disease (IBD). The monitoring of levels of IFX and anti-IFX antibodies is now considered part of the integral management. OBJECTIVE: To compare the clinical response according to a strictly clinical (CLN) or proactive (PRO) approach based on the monitoring of levels in week 14, in clinical practice. METHODS: We conducted a prospective study in IBD patients starting CT-P13. In the PRO group, levels of IFX and post-induction antibodies were systematically measured (week 14) and those with infraterapeutic levels (<3μg/ml) were intensified, irrespective of the clinical response. RESULTS: We included 77 patients (23 ulcerative colitis and 54 Crohn's disease). Both PRO (n=41) and CLN (n=36) groups showed initial and long-term efficacy without significant differences. At week 14, 61% clinical remission (CR) (58.5% PRO, 63.9% CLN) and 80.5% at least partial response (PR) (80.5% PRO, 80.6% CLN). In week 54, 68.8% CR (61% PRO, 77.8% CLN) and 76.6% at least PR (73.2% PRO, 80.6% CLN). Of the patients in CR in week 14 (24 PRO, 23 CLN), 13 of the PRO group were intensified due to infra-therapeutic levels. In this subgroup no significant differences were observed in secondary loss of response (PRO 0%, CLN 8.7%). CONCLUSION: Proactive management does not improve response or remission rates in the first year. The intensification of clinical remission patients with post-induction infratherapeutic levels does not seem to significantly prevent secondary loss of response in the first year


Assuntos
Humanos , Masculino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Medicamentos Biossimilares/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Estudos de Coortes , Infliximab/administração & dosagem , Infliximab/farmacologia , Estudos Prospectivos , Terapia Biológica , Estatísticas não Paramétricas , Fatores Imunológicos , Anti-Inflamatórios
12.
Aliment Pharmacol Ther ; 51(12): 1342-1352, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32379358

RESUMO

BACKGROUND: Virtual clinics represent a novel model of care in inflammatory bowel disease. Their effectiveness in promoting high quality use of biologic therapy and facilitating a treat-to-target approach is unknown. AIM: To evaluate clinical and process-driven outcomes in a virtual clinic compared to standard outpatient care amongst patients receiving intensified anti-TNF therapy for secondary loss of response. METHODS: We performed a retrospective multi-centre, parallel, observational cohort study of Crohn's disease patients receiving intensified anti-TNF therapy for secondary loss of response. Objective assessments of disease activity and anti-TNF trough levels at secondary loss of response and during subsequent 6-month semesters, were compared longitudinally between virtual clinic and standard outpatient care cohorts. The primary endpoint was treatment success, with appropriateness of dose intensification, tight disease monitoring and treatment de-escalation representing secondary outcomes. RESULTS: Of 149 patients with similar baseline characteristics, 69 were managed via a virtual clinic and 80 via standard outpatient care. There were higher rates of treatment success in the virtual clinic cohort (60.9 vs 35.0%, P < 0.002). Rates of appropriate dose intensification (82.6% vs 40.0%, P < 0.001), biomarker remission (faecal calprotectin P = 0.002), tight-disease monitoring (84.1% vs 28.8%, P < 0.001) and treatment de-escalation (21.3% vs 10.0%, P = 0.027) also favoured the virtual clinic cohort. CONCLUSION: This study favoured a virtual clinic-led model-of-care over standard outpatient care in facilitating treatment success as part of an effective treat-to-target approach in Crohn's disease. A virtual clinic model-of-care also improved treatment outcomes and quality of use of intensified anti-TNF therapy through processes that promoted appropriate dose intensification and tight-disease monitoring, while encouraging more frequent dose de-escalation.


Assuntos
Assistência Ambulatorial/métodos , Produtos Biológicos/administração & dosagem , Doença de Crohn/tratamento farmacológico , Planejamento de Assistência ao Paciente , Medicina de Precisão/métodos , Telemedicina/métodos , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial/normas , Produtos Biológicos/efeitos adversos , Estudos de Coortes , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Tolerância a Medicamentos , Feminino , Humanos , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente/normas , Medicina de Precisão/normas , Estudos Retrospectivos , Índice de Gravidade de Doença , Padrão de Cuidado , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologia , Adulto Jovem
14.
Rev. esp. enferm. dig ; 112(5): 360-366, mayo 2020. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-195589

RESUMO

INTRODUCTION: previous studies have shown that higher infliximab trough levels are associated with favorable shortterm and long-term therapeutic outcomes in inflammatory bowel disease. There is a need to determine which patients could benefit from proactive therapeutic drug monitoring in the induction phase. The aim of this study was to evaluate the pharmacokinetic variability of infliximab, determine the factors associated with achieving target infliximab trough levels in the induction phase and analyze the clinical and biochemical response at week 26 of treatment. PATIENTS AND METHODS: a retrospective observational study was performed of patients with inflammatory bowel disease and data available on serum levels of infliximab during the induction period. The percentage of patients that achieved target infliximab trough levels at week 6 was determined. Clinical remission and response and biochemical remission were evaluated at week 26. RESULTS: thirty patients were included and only 13 (43.3 %) had infliximab trough levels > 15 μg/mL at week 6. A clinical response was observed during the maintenance period in 71.4 % of patients, their infliximab levels were significantly higher than in non-responders (6.3 μg/mL [IQR: 6.7] vs 1.0 μg/mL [IQR: 5.0], respectively; p = 0.016). Likewise, 53.6 % of patients achieved biochemical remission (responders 6.2 μg/mL [IQR: 5.2] vs non-responders 3.2 μg/mL [IQR: 5.0]; p = 0.031). CONCLUSION: less than half of patients had target infliximab levels during the induction period. Therapeutic drug monitoring during this period is related to the achievement of therapeutic levels of infliximab and may lead to a better clinical response in these patients


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Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Infliximab/administração & dosagem , Infliximab/farmacocinética , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/farmacocinética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Estudos Retrospectivos , Indução de Remissão , Ensaio de Imunoadsorção Enzimática , Teorema de Bayes , Fatores de Tempo , Monitoramento de Medicamentos
15.
Aliment Pharmacol Ther ; 51(11): 1031-1038, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32329532

RESUMO

BACKGROUND: Biologic therapies in patients with Crohn's disease often yield low clinical and endoscopic remission rates. After multiple failed therapies, combining two biologic therapies is possibly the sole medical alternative to recurrent surgery. However, data on this approach are limited. AIMS: To assess the efficacy and safety of concomitant use of two biologic therapies in the largest cohort to date of refractory Crohn's disease patients. METHODS: Data were extracted from Crohn's disease patients started on dual biologic therapy at two referral centres. Biologics utilised include infliximab, adalimumab, vedolizumab, ustekinumab, certolizumab and golimumab. The primary outcome was endoscopic improvement (>50% reduction in Simplified Endoscopic Score-Crohn's disease [SES-CD] or explicitly stated). Endoscopic remission (SES-CD < 3 or stated), clinical response (Crohn's disease-patient-reported outcome-2 score [PRO2] reduced by 8), clinical remission (PRO2 < 8), and C-reactive protein (CRP) were also assessed. RESULTS: A total of 22 patients with 24 therapeutic trials of dual biologic therapy were identified. The majority of patients had prior surgical resections (91%), stricturing (59%) or penetrating (36%) phenotype, and perianal fistulas (50%). Median number of prior failed biologics was 4. Endoscopic improvement occurred in 43% of trials and 26% achieved endoscopic remission. Fifty per cent had clinical response and 41% achieved clinical remission. There were significant post-treatment reductions in median SES-CD (14.0 [12.0-17.5] to 6.0 [2.5-8.0], P = 0.0005], PRO-2 (24.1 [20.3-27.0] to 13.4 [4.6-21.8], P = 0.002] and CRP (17.0 [11.0-24.0] to 9.0 [4.0-14.0], P = 0.02). Presence of perianal fistulas decreased from 50% to 33%. Adverse events occurred in 13% of trials. CONCLUSION: Dual biologic therapy was associated with clinical, biomarker and endoscopic improvements in selected patients with refractory Crohn's disease who failed multiple biologics. Further studies are needed to validate this approach.


Assuntos
Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Doença de Crohn/tratamento farmacológico , Resistência a Medicamentos , Quimioterapia Combinada , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Adolescente , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Certolizumab Pegol/administração & dosagem , Certolizumab Pegol/efeitos adversos , Estudos de Coortes , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/metabolismo , Resistência a Medicamentos/efeitos dos fármacos , Quimioterapia Combinada/efeitos adversos , Endoscopia Gastrointestinal , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/efeitos adversos , Humanos , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Falha de Tratamento , Resultado do Tratamento , Ustekinumab/administração & dosagem , Ustekinumab/efeitos adversos , Adulto Jovem
16.
Clin Exp Immunol ; 201(1): 85-93, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32275772

RESUMO

Pulmonary sarcoidosis is characterized by an exaggerated CD4+ T cell response and formation of non-necrotizing granulomas. Tumour necrosis factor α (TNF-α) is regarded as crucial for granuloma formation and TNF-α inhibitors offer a third-line treatment option for patients not responding to conventional treatment. However, not all patients benefit from treatment, and an optimal dose and treatment duration have not been established. Insight into the influence of TNF-α inhibitors on lung immune cells may provide clues as to what drives inflammation in sarcoidosis and improve our understanding of treatment outcomes. To evaluate the effects of treatment with the TNF-α inhibitor infliximab on lung immune cells and clinical features of the patients, 13 patients with sarcoidosis refractory to conventional treatment were assessed with bronchoalveolar lavage (BAL), spirometry and computerized tomography (CT) scan closely adjacent to the start of infliximab treatment. These investigations were repeated after 6 months of treatment. Treatment with TNF-α inhibitor infliximab was well tolerated with no adverse events, except for one patient who developed a probable adverse event with liver toxicity. Ten patients were classified as responders, having a reduced CD4/CD8 ratio, a decreased percentage of CD4+ T cells expressing the activation marker CD69 and number of mast cells (P < 0·05 for all). The percentage of T regulatory cells (Tregs ), defined as forkhead box P3+ CD4+ T cells decreased in most patients. In conclusion, six months of infliximab treatment in patients with sarcoidosis led to signs of decreased CD4+ T cell alveolitis and decreased mastocytosis in the lungs of responders.


Assuntos
Infliximab/administração & dosagem , Pulmão/imunologia , Sarcoidose Pulmonar , Linfócitos T Reguladores/imunologia , Adulto , Lavagem Broncoalveolar , Relação CD4-CD8 , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Sarcoidose Pulmonar/tratamento farmacológico , Sarcoidose Pulmonar/imunologia , Sarcoidose Pulmonar/patologia , Fatores de Tempo , Tomografia Computadorizada por Raios X
17.
Medicine (Baltimore) ; 99(10): e18925, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150045

RESUMO

There is little consensus on the optimal timing of anti-tumor necrosis factor (anti-TNF) therapy to decrease the rates of hospitalization and surgery in Crohn disease (CD). We aimed to assess the real-world outcomes of anti-TNF therapy and estimate the optimal timing of anti-TNF therapy in Korean patients with CD.Claims data were extracted from the Korean Health Insurance Review and Assessment Service database. Incident patients diagnosed with CD between 2009 and 2016, with at least 1 anti-TNF drug prescription, and with follow-up duration > 6 months were stratified according to the number of relapses prior to initiation of anti-TNF therapy: groups A (≤1 relapse), B (2 relapses), C (3 relapses), and D (≥4 relapses). The cumulative survival curves free from emergency hospitalization (EH) and surgery were compared across groups.Among the 2173 patients analyzed, the best and worst prognoses were noted in groups A and D, respectively. The incidences of EH and surgery decreased significantly as the use of anti-TNF agents increased. The 5-year rate of hospitalization was significantly lower in group A than in groups C and D (P = .004 and .020, respectively), but similar between groups A and B. The 5-year rate of surgery was lower in group A than in group C (P = .024), but similar among groups A, B, and D.In Asian patients with CD, anti-TNF therapy reduces the risk of EH and surgery and should be considered before three relapses, regardless of disease duration.


Assuntos
Doença de Crohn/epidemiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/administração & dosagem , Adalimumab/uso terapêutico , Administração Oral , Doença de Crohn/tratamento farmacológico , Doença de Crohn/patologia , Doença de Crohn/cirurgia , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/uso terapêutico , Humanos , Incidência , Infliximab/administração & dosagem , Infliximab/uso terapêutico , Revisão da Utilização de Seguros , Masculino , Recidiva , República da Coreia/epidemiologia , Estudos Retrospectivos , Adulto Jovem
18.
Drugs Aging ; 37(5): 383-392, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32016824

RESUMO

BACKGROUND AND OBJECTIVE: Older people with inflammatory bowel disease (IBD) appear to have a lower response to anti-tumour necrosis factor (TNF) therapy, with more frequent complications than younger patients. The objective of this study was to assess persistence on therapy and the safety of anti-TNF therapy in older patients (aged ≥ 60 years). METHODS: We retrospectively reviewed the database of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD), extracting data regarding IBD patients aged ≥ 60 years and controls < 60 years of age at their first course of anti-TNF treatment. Data concerning persistence on therapy over the first year of treatment (primary objective) together with data on reasons for treatment withdrawal, concomitant diseases and treatments were collected. RESULTS: We identified 114 anti-TNF-naϊve patients aged ≥ 60 years (median age 64 years, range 60-80 years; 47 males) compared with 330 younger controls aged < 60 years (median age 39 years, range 18-59 years; 57 males). Older patients with Crohn's disease (n = 73) showed a significantly lower persistence with every kind of anti-TNF therapy (whether analysed together [p < 0.001] or separately for intravenous and subcutaneous [SC] therapy) than younger controls, whereas older patients with ulcerative colitis (n = 41) showed a lower persistence when combining all kinds of anti-TNF treatment (p = 0.004) and for SC therapy. Secondary failures, infections, and neoplasias, but not primary failure, occurred more frequently in older IBD patients than in younger controls. CONCLUSION: Despite a comparable number of primary failures, older IBD patients treated for the first time with anti-TNF agents showed lower treatment persistence due to higher rates of secondary failure, adverse events, infections, and tumours than younger patients in the first year of follow-up. The reasons for this difference still remain unclear.


Assuntos
Adalimumab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Suspensão de Tratamento/estatística & dados numéricos , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Estudos de Coortes , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de Tratamento
19.
Aliment Pharmacol Ther ; 51(6): 612-628, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31961001

RESUMO

BACKGROUND: Clinical application of therapeutic drug monitoring (TDM) to optimise anti-TNF therapies in patients with IBD depends upon target ranges. AIMS: To review methodology used to determine therapeutic ranges and critically compare and contrast its application to infliximab and adalimumab. METHODS: A systematic review was performed, and relevant literature was summarised and critically examined. RESULTS: Upper limits of the therapeutic range are determined by toxicity, a plateau response and cost. Lower limits are determined by optimal concentration on the target of action in vitro and/or in vivo, or by correlation of drug levels with clinical efficacy using area-under-receiver-operator-curve (AUROC) analysis. In 43 studies, there were huge variations in time at which infliximab and adalimumab levels were measured, the end-points used (clinical remission to mucosal healing), the clinical setting (active disease vs maintenance phase) and the reason for TDM (proactive vs reactive). In the maintenance phase for infliximab, lower trough limits 2.8-5.7 µg/mL are reported depending upon end-points used, with consistent AUROC 0.68-0.77. Adalimumab TDM targets are even less consistent with a lower limit 5.9-11.8 µg/mL (AUROC 0.66-0.83) in some studies, but no cut-off can be identified that is significantly associated with outcome in others, related to inherent pharmacokinetic and pharmacodynamic differences, and heterogeneity of study design. CONCLUSIONS: Evidence for exposure-response relationship is stronger for infliximab than adalimumab. Due to heterogeneity in settings for drug level measurements, therapeutic ranges vary. These factors need to be taken into account when interpreting the evidence and extending this to therapeutic strategies for IBD patients.


Assuntos
Adalimumab/administração & dosagem , Monitoramento de Medicamentos/normas , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/administração & dosagem , Adalimumab/efeitos adversos , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Infliximab/efeitos adversos , Valores de Referência , Resultado do Tratamento , Fator de Necrose Tumoral alfa/uso terapêutico , Cicatrização/efeitos dos fármacos
20.
Sci Rep ; 10(1): 511, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949246

RESUMO

Tight control management of Crohn's disease (CD) based on biomarkers is more effective than conventional clinical management; however, fecal calprotectin is not allowed in Asian and some Western countries. To investigate whether tight control management based on readily available serum biomarkers results in better outcomes, we retrospectively reviewed treatment courses of consecutive Japanese CD patients treated with anti-tumor necrosis factor agents between 2003 and 2018. The association between failure of tight control (C-reactive protein (CRP) ≥ 0.5 mg/dL or albumin (Alb) < 3.8 g/dL at week 8 or 24) and subsequent major adverse outcomes (MAOs; hospitalization related to CD worsening, surgery, and discontinuation due to treatment failure) were analyzed. Among 223 patients followed for >8 weeks, 88 patients experienced MAOs. Multivariate analysis identified penetrating type, CRP ≥ 0.5 mg/dL and Alb < 3.8 g/dL at week 8 as independent risk factors (hazard ratios: 2.16, 2.06, and 2.08, respectively). Among 204 patients followed for >24 weeks, 80 patients experienced MAOs. Penetrating type, CRP ≥ 0.5 mg/dL, and Alb < 3.8 g/dL at week 24 were identified as independent risk factors (2.39, 1.90, and 2.20, respectively). Even in settings without fecal calprotectin, tight control management based on serum CRP and Alb may help avoid MAOs.


Assuntos
Adalimumab/administração & dosagem , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Doença de Crohn/tratamento farmacológico , Infliximab/administração & dosagem , Albumina Sérica/metabolismo , Adalimumab/farmacologia , Adulto , Doença de Crohn/metabolismo , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Infliximab/farmacologia , Japão , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto Jovem
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