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1.
Medicine (Baltimore) ; 98(43): e17652, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651888

RESUMO

RATIONALE: Intestinal Behçet's disease (BD) is characterized by intestinal ulcerations and gastrointestinal symptoms. Ulcerative intestinal tuberculosis (TB) is usually with dyspepsia, abdominal pain, vomiting, and weight loss. The 2 diseases exhibit similar clinical manifestations, but the most critical aspects of their clinical courses and required treatments are not at all similar. PATIENT CONCERNS: We present a case in which a patient with intestinal Behçet's disease developed a de novo ulcerative intestinal TB infection after the start of anti-tumor necrosis factor-α treatment. This was despite histopathologic examination without caseous necrosis granuloma and negative for acid-fast staining and latent TB screen. DIAGNOSES: Intestinal Behçet's disease and intestinal TB. INTERVENTIONS: The patient was treated with quadruple antituberculous chemotherapy, comprising rifapentine, isoniazid, ethambutol, and pyrazinamide. OUTCOMES: At follow-up about 3 months, the therapy of oral antituberculous drugs and thalidomide was continued and the patient's condition had stabilized. LESSONS: This case illustrates the importance of closely monitoring patients who are on infliximab for possible onset of TB, even without abdominal symptoms, and with negative screening results for latent TB.


Assuntos
Síndrome de Behçet/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Infliximab/efeitos adversos , Tuberculose Gastrointestinal/induzido quimicamente , Adulto , Antituberculosos/uso terapêutico , Feminino , Humanos , Tuberculose Gastrointestinal/tratamento farmacológico
3.
Expert Opin Pharmacother ; 20(17): 2161-2168, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31574236

RESUMO

Introduction: Crohn's disease (CD) is a chronic inflammatory condition that can occur throughout the gastrointestinal tract. The aims of treatment of children with CD are to induce and maintain clinical remission of disease, optimize nutrition and growth, minimize adverse effects of therapies, and if possible, achieve mucosal healing.Areas covered: This review summarizes evidence for the various therapeutic options in the treatment of children with CD. Exclusive enteral nutrition, corticosteroids, and biologics may be used for induction of remission. Immunomodulators (thiopurines, methotrexate) and biologics (infliximab, adalimumab) may be employed for maintenance of remission to prevent flares of disease and avoid chronic steroid use. In cases of fibrotic disease, intestinal perforations, or medically refractory, surgery may be the best therapeutic option.Expert opinion: Exclusive enteral nutrition, corticosteroids, and biologics (including anti-TNF inhibitors) may be used for induction of remission in patients with active flare of their disease. Immunomodulators and TNF inhibitors may be used for maintenance of remission. Early use of anti-TNF inhibitors in patients with moderate to severe CD may improve efficacy and prevent penetrating complications of disease. While pediatric data is limited, newer biologics, such as vedolizumab and ustekinumab, are used off-label in anti-TNF refractory disease.


Assuntos
Adalimumab/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Infliximab/uso terapêutico , Adalimumab/efeitos adversos , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Criança , Ensaios Clínicos como Assunto , Humanos , Fatores Imunológicos/efeitos adversos , Infliximab/efeitos adversos , Indução de Remissão
4.
Intern Med ; 58(18): 2703-2709, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31527369

RESUMO

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by reactivation of the JC virus under an immunosuppressed state. This condition carries a high risk of cryptococcal meningitis. We herein report a 65-year-old woman who simultaneously developed PML and cryptococcal meningitis and presented with bilateral sixth nerve palsy. She had been treated with methotrexate and infliximab for rheumatoid arthritis. Her symptoms improved with antifungal drug treatment and discontinuation of immunosuppression therapy. Although concurrent PML and cryptococcal meningitis is rare, it should be considered in immunosuppressed patients.


Assuntos
Antifúngicos/uso terapêutico , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Imunossupressão/efeitos adversos , Infliximab/efeitos adversos , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Meningite Criptocócica/tratamento farmacológico , Metotrexato/efeitos adversos , Idoso , Antirreumáticos/uso terapêutico , Feminino , Humanos , Infliximab/uso terapêutico , Vírus JC/isolamento & purificação , Leucoencefalopatia Multifocal Progressiva/etiologia , Meningite Criptocócica/etiologia , Metotrexato/uso terapêutico , Resultado do Tratamento
5.
J Drugs Dermatol ; 18(8): 828-830, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31424716

RESUMO

A 56-year-old Caucasian male with a history of chronic plaque psoriasis, primary sclerosing cholangitis status-post liver transplant on tacrolimus, and ulcerative colitis on infliximab developed a progressive erythematous eruption with associated fatigue, anorexia, myalgias, and arthralgias. On two separate occasions, his skin biopsy demonstrated a lichenoid interface dermatitis (LID). Despite multiple courses of oral prednisone, topical steroids, and a short course of hydroxychloroquine, his symptoms continued to relapse and remit. When a temporal association between increasing his infliximab dose and the global progression of his disease was identified, he was ultimately diagnosed with a TNF-α inhibitor-induced psoriasis flare. Despite the patient's long-standing history of psoriasis, a plausible psoriasis rebound reaction after systemic steroids was not strongly considered in light of his histopathology. Though lichenoid interface dermatitis is a commonly reported histologic finding in patients on TNF-α inhibitors, it has scarcely been reported in patients with psoriasiform eruptions clinically.


Assuntos
Erupção por Droga/diagnóstico , Infliximab/efeitos adversos , Erupções Liquenoides/diagnóstico , Psoríase/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Biópsia , Diagnóstico Diferencial , Erupção por Droga/etiologia , Erupção por Droga/patologia , Humanos , Erupções Liquenoides/patologia , Masculino , Pessoa de Meia-Idade , Psoríase/diagnóstico , Pele/efeitos dos fármacos , Pele/patologia , Exacerbação dos Sintomas
7.
Drugs ; 79(10): 1053-1063, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31183768

RESUMO

The inflammatory bowel diseases commonly affect individuals during their peak reproductive years. Patients are often concerned about the impact of medical therapies on their ability to conceive, effect on the fetus, as well as the ability to breastfeed, which has led to poor medical adherence during pregnancy. However, most medications are safe, and discontinuation may lead to active disease, which is associated with adverse materno-fetal outcomes. The anti-TNF biologic therapies, infliximab and adalimumab have been extensively studied in the context of pregnancy. They are actively transferred to the placenta during the second and third trimesters; these have not been associated with an increased rate of congenital abnormalities or fetal death. The minimal amounts of drug that are transferred to breast milk are proteolyzed by the infant's digestive system with no reported short- or long-term adverse effects. There is a paucity of clinical data for the other approved anti-TNF agents or newer anti-integrin (vedolizumab) and anti-interleukin (ustekinumab) therapies used in the management of inflammatory bowel disease; however, no significant safety signals have been documented thus far. The new oral small molecule therapy, tofacitinib is teratogenic in animal models and is contra-indicated in patients attempting pregnancy. It is important that patients, as well as physicians managing patients with these conditions, be aware of the impact of these medical therapies during pregnancy.


Assuntos
Adalimumab/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/administração & dosagem , Ustekinumab/administração & dosagem , Adalimumab/efeitos adversos , Administração Oral , Anticorpos Monoclonais Humanizados/efeitos adversos , Aleitamento Materno , Desenvolvimento Infantil/efeitos dos fármacos , Feminino , Humanos , Recém-Nascido , Infliximab/efeitos adversos , Leite Humano/química , Leite Humano/metabolismo , Gravidez , Transdução de Sinais , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ustekinumab/efeitos adversos
8.
BMJ Case Rep ; 12(4)2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31036734

RESUMO

We report a 36-year-old man who developed a large epidural and paraspinal abscess as a complication of infliximab therapy being used for underlying Crohn's disease. Cultures of the collection grew methicillin-susceptible Staphylococcus aureus, and treatment consisted of abscess drainage, prolonged intravenous and oral flucloxacillin and temporary withholding of his infliximab. While infection-related complications are well described with infliximab therapy, this is the first description of a large paraspinal abscess with epidural extension.


Assuntos
Abscesso/microbiologia , Doença de Crohn/tratamento farmacológico , Espaço Epidural/microbiologia , Infliximab/efeitos adversos , Abscesso/diagnóstico por imagem , Abscesso/tratamento farmacológico , Abscesso/cirurgia , Adulto , Antibacterianos/uso terapêutico , Anticorpos Monoclonais , Doença de Crohn/complicações , Drenagem/métodos , Espaço Epidural/diagnóstico por imagem , Floxacilina/administração & dosagem , Floxacilina/uso terapêutico , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/uso terapêutico , Humanos , Infliximab/uso terapêutico , Masculino , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/isolamento & purificação , Resultado do Tratamento
9.
Ir Med J ; 3(112): 902, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-31124350

RESUMO

Aim To report the first case of cardiac tamponade related to Infliximab induction therapy in an Ulcerative Colitis patient. Methods Review of published case reports. Results This complication was likely due to a type 3 hypersensitivity immune-complex reaction resulting in a reactive pericardial effusion Discussion Though rare, this case demonstrates how autoimmune reaction to anti-TNF𝛼 therapy can initially mimic infection, as our patient presented with tachycardia, hypotension, raised inflammatory and infective markers and fever.


Assuntos
Tamponamento Cardíaco/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Infliximab/efeitos adversos , Autoimunidade , Tamponamento Cardíaco/diagnóstico , Tamponamento Cardíaco/imunologia , Tamponamento Cardíaco/terapia , Colite Ulcerativa/imunologia , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/imunologia , Humanos , Infliximab/administração & dosagem , Infliximab/imunologia , Pessoa de Meia-Idade , Derrame Pericárdico/induzido quimicamente , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/imunologia , Derrame Pericárdico/terapia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologia
10.
World J Gastroenterol ; 25(18): 2240-2250, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31143074

RESUMO

BACKGROUND: When opportunistic infections occur, patients with inflammatory bowel disease (IBD) commonly display a significantly increased rate of morbidity and mortality. With increasing use of immunosuppressive agents and biological agents, opportunistic infections are becoming a hot topic in the perspective of drug safety in IBD patients. Despite the well-established role of opportunistic infections in the prognosis of IBD patients, there are few epidemiological data investigating the incidence of opportunis-tic infections in IBD patients in China. Besides, the risk factors for opportunistic infection in Chinese IBD patients remain unclear. AIM: To predict the incidence of opportunistic infections related to IBD in China, and explore the risk factors for opportunistic infections. METHODS: A single-center, prospective study of IBD patients was conducted. The patients were followed for up to 12 mo to calculate the incidence of infections. For each infected IBD patient, two non-infected IBD patients were selected as controls. A conditional logistic regression analysis was used to assess associations between putative risk factors and opportunistic infections, which are represented as odds ratios (OR) and 95% confidence intervals (CIs). RESULTS: Seventy (28.11%) out of 249 IBD patients developed opportunistic infections. Clostridium difficile infections and respiratory syncytial virus infections were found in 24 and 16 patients, respectively. In a univariate analysis, factors such as the severity of IBD, use of an immunosuppressant or immunosuppressants, high levels of fecal calprotectin, and C-reactive protein or erythrocyte sedimentation rate were individually related to a significantly increased risk of opportunistic infection. Multivariate analysis indicated that the use of any immunosuppressant yielded an OR of 3.247 (95%CI: 1.128-9.341), whereas the use of any two immunosuppressants yielded an OR of 6.457 (95%CI: 1.726-24.152) for opportunistic infection. Interestingly, when immunosuppressants were used in combination with infliximab (IFX) or 5-aminosalicylic acid, a significantly increased risk of opportunistic infection was also observed. The relative risk of opportunistic infection was greatest in IBD patients with severe disease activity (OR = 9.090; 95%CI: 1.532-53.941, relative to the remission stage). However, the use of IFX alone did not increase the risk of opportunistic infection. CONCLUSION: Factors such as severe IBD, elevated levels of fecal calprotectin, and the use of immunosuppressive medications, especially when used in combination, are major risk factors for opportunistic infections in IBD patients. The use of IFX alone does not increase the risk of opportunistic infection.


Assuntos
Doenças Inflamatórias Intestinais/complicações , Infecções Oportunistas/epidemiologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , China/epidemiologia , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Fezes/química , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Incidência , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/imunologia , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Complexo Antígeno L1 Leucocitário/análise , Masculino , Mesalamina/administração & dosagem , Mesalamina/efeitos adversos , Mesalamina/uso terapêutico , Pessoa de Meia-Idade , Infecções Oportunistas/complicações , Infecções Oportunistas/imunologia , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
11.
Int J Mol Sci ; 20(10)2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126015

RESUMO

Inflammatory bowel disease (IBD) presents with disabling symptoms and may lead to insufficient growth and late pubertal development in cases of disease onset during childhood or adolescence. During the last decade, the role of anti-tumor necrosis factor (TNF) in the treatment of paediatric-onset IBD has gained more ground. The number of biologicals presently available for children and adolescents with IBD has increased, biosimilars have become available, and practices in adult gastroenterology with regards to anti-TNF have changed. The aim of this study is to review the current evidence on the indications, judicious use, effectiveness and safety of anti-TNF agents in paediatric IBD. A PubMed literature search was performed and included articles published after 2000 using the following terms: child or paediatric, Crohn, ulcerative colitis, inflammatory bowel disease, anti-TNF, TNF alpha inhibitor, infliximab, adalimumab, golimumab and biological. Anti-TNF agents, specifically infliximab and adalimumab, have proven to be effective in moderate and severe paediatric IBD. Therapeutic drug monitoring increases therapy effectiveness and safety. Clinical predictors for anti-TNF response are currently of limited value because of the variation in outcome definitions and follow-ups. Future research should comprise large cohorts and clinical trials comparing groups according to their risk profile in order to provide personalized therapeutic strategies.


Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Adalimumab/efeitos adversos , Adolescente , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Criança , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Humanos , Infliximab/efeitos adversos , Fator de Necrose Tumoral alfa/antagonistas & inibidores
12.
Dermatol Ther ; 32(3): e12917, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30994249

RESUMO

Infliximab is a tumor necrosis factor-alpha (TNF-a) inhibitor widely used in the treatment of moderate to severe chronic plaque psoriasis. Here, we report a case of vitiligo following infliximab administration in a patient with chronic plaque psoriasis. The case serves as a reminder of vitiligo induced by TNF-a-antagonist therapy.


Assuntos
Infliximab/efeitos adversos , Psoríase/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Vitiligo/induzido quimicamente , Adulto , Doença Crônica , Humanos , Masculino
13.
Medicine (Baltimore) ; 98(15): e15189, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30985712

RESUMO

To determine the effect of prior corticosteroid treatment on the results of infliximab (IFX) therapy in patients with Crohn disease (CD).Patients with CD treated with at least 3 IFX infusions between March 2009 and April 2017 were divided into steroid group (n = 43) and nonsteroid group (n = 22) and analyzed retrospectively.The cumulative probabilities of clinical remission and response to IFX at weeks 14, 30, 54, and 78 were higher in the steroid group, though this difference was not statistical significant. At the mean interval of 11.7 months following the initiation of IFX treatment, the mucosal healing rate was significantly higher in the steroid group (71.0% vs 22.2%, P < .01). There was no statistical difference in the incidence of adverse reactions between the 2 groups.In CD, patients with prior corticosteroid treatment may increase the response rate to IFX therapy.


Assuntos
Corticosteroides/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Infliximab/uso terapêutico , Adolescente , Adulto , Feminino , Fármacos Gastrointestinais/efeitos adversos , Humanos , Infliximab/efeitos adversos , Masculino , Prednisona/uso terapêutico , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
14.
World J Gastroenterol ; 25(12): 1465-1477, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30948910

RESUMO

BACKGROUND: Anti-tumor necrosis factor α (TNFα) represents the best therapeutic option to induce mucosal healing and clinical remission in patients with moderate-severe ulcerative colitis. On the other side gut microbiota plays a crucial role in pathogenesis of ulcerative colitis but few information exists on how microbiota changes following anti-TNFα therapy and on microbiota role in mucosal healing. AIM: To elucidate whether gut microbiota and immune system changes appear following anti TNFα therapy during dextran sulfate sodium (DSS) colitis. METHODS: Eighty C57BL/6 mice were divided into four groups: "No DSS", "No DSS + anti-TNFα", "DSS" and "DSS + anti-TNFα". "DSS" and "DSS + anti-TNFα" were treated for 5 d with 3% DSS. At day 3, mice whithin "No DSS+anti-TNFα" and "DSS+anti-TNFα" group received 5 mg/kg of an anti-TNFα agent. Forty mice were sacrificed at day 5, forty at day 12, after one week of recovery post DSS. The severity of colitis was assessed by a clinical score (Disease Activity Index), colon length and histology. Bacteria such as Bacteroides, Clostridiaceae, Enterococcaceae and Fecalibacterium prausnitzii (F. prausnitzii) were evaluated by quantitative PCR. Type 1 helper T lymphocytes (Th1), type 17 helper T lymphocytes (Th17) and CD4+ regulatory T lymphocytes (Treg) distributions in the mesenteric lymph node (MLN) were studied by flow cytometry. RESULTS: Bacteria associated with a healthy state (i.e., such as Bacteroides, Clostridiaceae and F. prausnitzii) decreased during colitis and increased in course of anti-TNFα treatment. Conversely, microorganisms belonging to Enterococcaceae genera, which are linked to inflammatory processes, showed an opposite trend. Furthermore, in colitic mice treated with anti-TNFα microbial changes were associated with an initial increase (day 5 of the colitis) in Treg cells and a consequent decrease (day 12 post DSS) in Th1 and Th17 frequency cells. Healthy mice treated with anti-TNFα showed the same histological, microbial and immune features of untreated colitic mice. "No DSS + anti-TNFα" group showed a lymphomononuclear infiltrate both at 5th and 12th d at hematoxylin and eosin staining, an increase of in Th1 and Th17 frequency at day 12, an increase of Enterococcaceae at day 5, a decrease of Bacteroides and Clostridiaceae at day 12. CONCLUSION: Anti-TNFα treatment in experimental model of colitis improves disease activity but it is associated to an increase in Th17 pathway together with gut microbiota alteration.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Bactérias/efeitos dos fármacos , Bactérias/imunologia , Bactérias/isolamento & purificação , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/imunologia , Colo/efeitos dos fármacos , Colo/imunologia , Colo/microbiologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Microbioma Gastrointestinal/imunologia , Humanos , Infliximab/efeitos adversos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Índice de Gravidade de Doença , Células Th17/imunologia , Fator de Necrose Tumoral alfa/imunologia
15.
Lancet ; 393(10182): 1699-1707, 2019 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-30929895

RESUMO

BACKGROUND: The infliximab biosimilar CT-P13 was approved for use in Crohn's disease after clinical comparison with originator infliximab in ankylosing spondylitis and rheumatoid arthritis; however, concerns about such indication extrapolation have been expressed. This study investigated whether CT-P13 is non-inferior to infliximab in patients with Crohn's disease who were naive to biological therapy. METHODS: In this randomised, multicentre, double-blind, phase 3 non-inferiority study, we enrolled patients with active Crohn's disease who had not responded to, or were intolerant to, non-biological treatments. Patients were randomly assigned (1:1:1:1) to receive CT-P13 then CT-P13, CT-P13 then infliximab, infliximab then infliximab, or infliximab then CT-P13, with switching occurring at week 30. Patients received 5 mg/kg CT-P13 or infliximab at weeks 0, 2, 6, and then every 8 weeks up to week 54. The primary endpoint was the proportion of patients with a decrease of 70 points or more in Crohn's Disease Activity Index (CDAI) from baseline to week 6. A non-inferiority margin of -20% was set (CT-P13 was non-inferior to infliximab if the lower limit of the two-sided 95% CI for the treatment difference was greater than -20). This trial is registered with ClinicalTrials.gov, number NCT02096861, and is completed. FINDINGS: Between Aug 20, 2014, and Feb 15, 2017, 308 patients were assessed for eligibility, and 220 patients were enrolled: 111 were randomly assigned to initiate CT-P13 (56 to the CT-P13-CT-P13 group and 55 to the CT-P13-infliximab group) and 109 to initiate infliximab (54 to the infliximab-infliximab group and 55 to the infliximab-CT-P13 group). CDAI-70 response rates at week 6 were similar for CT-P13 (77 [69·4%, 95% CI 59·9 to 77·8] of 111) and infliximab (81 [74·3%, 95% CI 65·1 to 82·2] of 109; difference -4·9% [95% CI -16·9 to 7·3]), thereby establishing non-inferiority. Over the total study period, 147 (67%) patients experienced at least one treatment-emergent adverse event (36 [64%] in the CT-P13-CT-P13 group, 34 [62%] in the CT-P13-infliximab group, 37 [69%] in the infliximab-infliximab group, and 40 [73%] in the infliximab-CT-P13 group). INTERPRETATION: This study showed non-inferiority of CT-P13 to infliximab in patients with active Crohn's disease. Biosimilar CT-P13 could be a new option for the treatment of active Crohn's disease. FUNDING: Celltrion, Pfizer.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Infliximab/uso terapêutico , Adulto , Anticorpos Monoclonais/efeitos adversos , Medicamentos Biossimilares/efeitos adversos , Método Duplo-Cego , Substituição de Medicamentos , Feminino , Fármacos Gastrointestinais/efeitos adversos , Humanos , Infliximab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
16.
J Pharmacol Sci ; 139(4): 289-303, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30922656

RESUMO

PURPOSE: This network meta-analysis was aimed to enhance the corresponding evidence with respect to the efficacy and safety of biologic treatments. METHODS: PubMed and EMBASE database searches were conducted. Odds ratios were used to evaluate multi-aspect comparisons. SUCRA was used to analyze the ranking of treatments in each endpoint. Psoriasis Area and Severity Index 50%, 75%, 90%, 100%, PGA, dermatology quality of life index were considered as outcomes while adverse events and discontinuation were adopted to evaluate safety. RESULTS: For safety issues, briakinumab was associated with least headache and itolizumab had the lowest risk of infection. Ustekinumab performed best in discontinuation. SUCRA ranked briakinumab, brodalumab, Infliximab and ixekizumab as the favorable efficacy therapies, while briakinumab and brodalumab seemed to have mild side effects. No heterogeneity was observed between these comparisons. CONCLUSIONS: Briakinumab performed relatively stable under efficacy and safety outcome. Infliximab can be a good choice for its lower risk of infection. Brodalumab present very good potential in efficacy outcome like PASI and PGA. More clinical trials are required to supply more data about discontinuation of infliximab and infection of brodalumab and larger RCT for assessment of briakinumab.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Infliximab/uso terapêutico , Psoríase/tratamento farmacológico , Ustekinumab/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Bases de Dados Bibliográficas , Infliximab/efeitos adversos , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento , Ustekinumab/efeitos adversos
17.
Dig Dis Sci ; 64(7): 1952-1958, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30815825

RESUMO

BACKGROUND: Tumor necrosis factor antagonists (TNFs) are effective for moderate-severe Crohn's disease (CD). Approximately one-third of patients have primary-nonresponse to TNFs, which is reported to predict worse response to subsequent TNF therapy. However, this is based on treatment with subcutaneously (SC) administered, fixed-dose TNFs after failure of intravenously (IV) administered, weight-based TNFs. No study has specifically assessed the clinical and endoscopic effectiveness of IV TNFs following primary-nonresponse to SC TNFs. We hypothesize that IV, weight-based TNF dosing offers advantages over SC, fixed-dose TNFs and may be effective despite primary-nonresponse to previous SC fixed-dose TNFs. METHODS: This retrospective cohort study identified patients with moderate-severe CD with primary-nonresponse to one or more SC TNFs who subsequently received the IV TNF, infliximab for ≥ 12 weeks. We described baseline characteristics, and clinical, endoscopic and biochemical response to therapy. RESULTS: Key characteristics of 17 patients are described in Table 1. After ≥ 12 weeks of infliximab, 11 of 15 (73.3%) patients with clinical data reported clinical response and remission. Of 11 patients with endoscopic data, restaging colonoscopy revealed mucosal improvement in seven (63.6%) patients. Of these, five (45.5%) had endoscopic remission and three (27.3%) had mucosal healing. Table 1 Baseline characteristics of CD patients with primary-nonresponse to subcutaneous (SC) tumor necrosis antagonists (TNF), subsequently treated with intravenous (IV) TNF therapy Characteristics N 17 Mean age, years (range) 37.5 (18-67) Mean BMI, kg/m2 (range) 26.6 (17.8-40.6) Mean albumin prior to infliximab, g/dL (range) RR: 3.5-5.2 g/dL 3.57 (2.5-4.2) Female sex [n (%)] 7 (41.2) Tobacco use [n (%)]  Never 15 (88.2)  Former 1 (5.88)  Current 1 (5.88) Age at diagnosis [n (%)]  Less than 17 2 (11.8)  17-40 11 (64.7)  Over 40 4 (23.5) Mean disease duration, yrs (range) 7.76 (1-24) Disease extent [n (%)]  Ileal 2 (11.8)  Colonic 5 (29.4)  Ileocolonic 10 (64.7) Disease behavior [n (%)]  Nonstenosing, nonpenetrating 10 (58.8)  Stenosing 3 (17.6)  Penetrating 2 (11.8)  Stenosing and penetrating 2 (11.8) History of gastrointestinal surgery [n (%)] 4 (23.5)  Ileocecal resection (n) 2  Hemicolectomy (n) 2 Prior therapy [n (%)]  IV corticosteroids 3 (17.6)  Oral corticosteroids 14 (82.4)  5-ASA 12 (70.6)  Thiopurine 14 (82.4)  Methotrexate 10 (58.8) Prior biologic therapy  Adalimumab only 12 (70.6)  Certolizumab pegol only 2 (11.8)  Adalimumab and certolizumab pegol 2 (11.8)  Adalimumab, certolizumab pegol and golimumab 1 (5.88) Dose escalation of prior SC TNF [n (%)]  Adalimumab 9 (52.9)  Certolizumab pegol 0 (0.0)  Golimumab 0 (0.0) During infliximab, concomitant therapy [n (%)]  Immunomodulator 13 (76.5)  Corticosteroid 5 (29.4) CONCLUSIONS: Patients with moderate-severe CD with prior primary-nonresponse to SC, fixed-dose TNFs, subsequently treated with IV, weight-based TNF have high rates of clinical and endoscopic response and remission. Therefore, despite primary-nonresponse to SC TNFs, patients may benefit from IV TNF therapy and may not require a change to a different class of biologic therapy.


Assuntos
Produtos Biológicos/administração & dosagem , Doença de Crohn/tratamento farmacológico , Infliximab/administração & dosagem , Mucosa Intestinal/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Administração Intravenosa , Adolescente , Adulto , Idoso , Produtos Biológicos/efeitos adversos , Doença de Crohn/diagnóstico , Doença de Crohn/imunologia , Feminino , Humanos , Infliximab/efeitos adversos , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologia , Cicatrização/efeitos dos fármacos , Adulto Jovem
18.
Drug Des Devel Ther ; 13: 791-805, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880912

RESUMO

Background: Infliximab (Remicade), a chimeric monoclonal antibody against human TNFα, will inevitably face competition from biosimilar products, because of its effectiveness in autoimmune diseases and rapidly increasing market demand. According to guidelines for biosimilar development, the "biosimilar-expression system" may differ from that of the innovator, but more appropriate studies should be carried out to demonstrate the comparability between biosimilar and innovator. CMAB008 is an infliximab biosimilar candidate developed by the State Key Laboratory of Antibody Medicine and Targeted Therapy of China. Infliximab was expressed in SP2/0 cells, while CMAB008 was produced in a CHO-expression system. Methods: In this study, infliximab and CMAB008 were compared on physicochemical and biological characterizations, including protein content, activity, physiochemical integrity, impurities, additives, and immunogenicity. Results: The results showed that they were highly similar and comparable, except some differences in glycosylation. As glycosylation profiles can influence immunogenicity and occurrence of allergy or other adverse reactions of antibody therapeutics, primary tolerability and pharmacokinetics of CMAB008 were evaluated. In the phase I clinical trial, plasma concentration of CMAB008 and antidrug antibodies were also measured using ELISA and bridging ELISA, respectively. CMAB008 exhibited favorable clinical tolerability, no adverse events in the 3 mg/kg single-dose group (recommended therapeutic dosage), and no serious adverse events in the multiple-dose group. Also, no injection-site reactions were observed in the experiment. Conclusion: In summary, CMAB008 might have the potential to be an effective drug compared with infliximab.


Assuntos
Infliximab/química , Infliximab/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Química Física , Voluntários Saudáveis , Humanos , Infliximab/efeitos adversos , Infliximab/farmacocinética , Injeções Intravenosas , Camundongos , Camundongos Endogâmicos , Modelos Animais
19.
Rev Med Suisse ; 15(644): 668-671, 2019 Mar 27.
Artigo em Francês | MEDLINE | ID: mdl-30916904

RESUMO

Anti-TNFs have revolutionized the management of numerous chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Although anti-TNF drugs are highly effective, 2-5 % of treated patients develop psoriasis-like skin lesions called paradoxical psoriasis. Paradoxical psoriasis is specific to anti-TNFs and it is, despite clinically resembling classical psoriasis, immunologically distinct. As it frequently requires cessation of the anti-TNF therapy, paradoxical psoriasis is a critical drug side effect and a challenge in the management of patients with chronic inflammatory diseases. In this review, we discuss the clinical, histological and pathogenic distinctions between the two entities and the management of patients developing paradoxical psoriasis.


Assuntos
Doenças Inflamatórias Intestinais , Psoríase , Fator de Necrose Tumoral alfa , Adalimumab/efeitos adversos , Adalimumab/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/efeitos adversos , Infliximab/uso terapêutico , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores
20.
Med Sci Monit ; 25: 2257-2264, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30917108

RESUMO

BACKGROUND This study investigated the risk factors of infliximab (IFX)-related infusion reactions (IR) in Chinese patients with inflammatory bowel disease (IBD). MATERIAL AND METHODS The medical records of 330 consecutive IBD patients treated with IFX between 2009 and 2017 were reviewed. The incidence of IR and adverse effects were recorded in detail, and the potential risk factors related to IR were analyzed by univariate and logistic regression analysis. RESULTS The 330 patients received a total of 2108 IFX infusions, with a median follow-up of 29 months. Eighteen patients (5.5%) experienced IR: 15 were immediate (2 severe) and 3 were late (0 severe). The patients who were treated with episodic IFX without concomitant IM therapy and at the 2nd IFX series (all P<0.001) had higher incidence of IR. Logistic regression revealed the 2nd IFX treatment series (OR=0.017, P<0.001) and episodic use of IFX (OR=0.113, P<0.001) as the significant predictors. Antibodies against infliximab (ATI) were highly positive in 10 of 14 patients (71%) with IR. Sixty-seven percent of patients finished infusions after IR through appropriate management. CONCLUSIONS IFX infusions were accompanied by IR in about 5% of Chinese IBD patients. Severe IR was rare. The patients with the 2nd series or episodic use of IFX should be monitored closely during infusion.


Assuntos
Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/efeitos adversos , Adolescente , Adulto , Anticorpos Monoclonais/uso terapêutico , Grupo com Ancestrais do Continente Asiático/genética , China , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Seguimentos , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/fisiopatologia , Infliximab/uso terapêutico , Reação no Local da Injeção/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
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