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1.
Clin Exp Rheumatol ; 37 Suppl 121(6): 137-141, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31856941

RESUMO

OBJECTIVES: Initial recommendations on anti-TNF treatment for Behçet's disease (BD) included an intravenous infliximab infusion for acute posterior uveitis to achieve a fast-onset response. We aimed to examine the long-term outcome of our patients with acute sight-threatening BD who received successful short-term treatment with infliximab. METHODS: We performed a retrospective longitudinal outcome study including consecutive patients who responded to one infliximab infusion (5mg/kg) for BD-associated acute posterior uveitis or panuveitis, followed, or not, by one or two additional infusions. RESULTS: Twelve patients (aged 51±14 years, mean±SD, 67% men) with bilateral (n=9) or unilateral (n=3) ocular attack (relapsing in 9 patients) achieved resolution of ocular inflammation within 4 weeks after the first infusion of infliximab, given as add-on to azathioprine (n=9) or to azathioprine/cyclosporine combination. Ten of 12 patients received a second infusion at 4 weeks and 9 of them received a third infusion at 8 weeks from baseline. Except from a patient who relapsed after 6 months and responded to infliximab re-treatment, 11 patients remain ocular relapse-free during follow-up, ranging from 4 to 16 years (10±4). Five patients (45%) discontinued azathioprine being in full BD remission and remain any drug-free at end of follow-up. CONCLUSIONS: Successful short-term infliximab treatment combined with conventional immunosuppressives for BD-associated sight-threatening uveitis may lead to remission for many years thereafter. This observation may suggest that infliximab as a first-line therapy should be promptly administered to every patient with ocular BD for rapid remission of ocular inflammation and preservation of visual acuity.


Assuntos
Síndrome de Behçet , Infliximab/uso terapêutico , Uveíte , Adulto , Idoso , Anticorpos Monoclonais , Síndrome de Behçet/tratamento farmacológico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Uveíte/tratamento farmacológico
2.
Rev Med Suisse ; 15(671): 2105-2108, 2019 Nov 13.
Artigo em Francês | MEDLINE | ID: mdl-31742942

RESUMO

Screening for latent tuberculosis infection (LTI) is recommended in immunosuppressed patients due to an increased risk of progression from LTI to active tuberculosis. Screening involves indirect immunological tests such as the tuberculin skin test (TST) and the interferon-y release assays (IGRAs). IGRAs seem to show superior performance compared to TST in screening for LTI. However, their use and interpretation in immunosuppressed patients is questionable, particularly because of an increased number of false negative or indeterminate results and a low agreement between tests. Presently, there are no swiss national recommendations for their use in immunosuppressed -patients, except for candidates to anti-TNF treatment.


Assuntos
Hospedeiro Imunocomprometido , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/microbiologia , Tuberculose Latente/complicações , Tuberculose Latente/diagnóstico , Humanos , Testes de Liberação de Interferon-gama , Sensibilidade e Especificidade , Teste Tuberculínico , Fator de Necrose Tumoral alfa/antagonistas & inibidores
3.
Medicine (Baltimore) ; 98(44): e17768, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689839

RESUMO

Relapsing polychondritis (RP) is a rare immune-mediated disease affecting cartilaginous structures. Respiratory tract manifestations are frequent and constitute a major cause of morbidity and mortality. The present review of the literature was designed to assess the efficacy of tumor necrosis factor alpha (TNF-α) inhibitors in respiratory tract involvement of RP.A MEDLINE literature search was performed from January 2000 to December 2016 to identify all studies and case reports of anti-TNF-α therapy in RP. Articles published in English or French concerning patients with respiratory tract involvement were eligible. Two authors (JB, FL) independently reviewed and extracted data concerning each patient and 2 personal cases were added. Treatment efficacy was assessed according to systemic and/or respiratory criteria.A total of 28 patients (mean age: 41.6 years; 16 females/12 males) were included in the final analysis. Anti-TNF-α therapy was associated with improved health status and respiratory symptoms in 67.8% and 60.1% of cases, respectively.These results suggest that TNF-α inhibitors could be considered for the treatment of respiratory tract involvement of RP.


Assuntos
Antirreumáticos/uso terapêutico , Policondrite Recidivante/tratamento farmacológico , Doenças Respiratórias/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Policondrite Recidivante/complicações , Sistema Respiratório/efeitos dos fármacos , Doenças Respiratórias/etiologia , Resultado do Tratamento
4.
Expert Opin Drug Metab Toxicol ; 15(11): 913-925, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31623470

RESUMO

Introduction: The treatment of psoriasis with conventional topical therapies and disease-modifying anti-rheumatic drugs (DMARDs) is often linked to unsatisfactory outcomes and the risk of serious adverse events. Over the last decades, research advances in understanding the role of tumor necrosis factor alpha (TNF α) and other cytokines in the pathogenesis of psoriasis have driven the introduction of biologic agents targeting specific immune mediators in everyday clinical practice. TNF α inhibitors are a consolidated treatment option for patients with moderate-to-severe disease with remarkable efficacy and a reassuring safety profile.Areas covered: The PubMed database was searched using combinations of the following keywords: psoriasis, TNF α inhibitors, biologic therapy, pharmacodynamics, adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, adverse effects. The aim of this review is to describe the pharmacodynamic profile of anti-TNF α inhibitors, currently approved by the European Medicines Agency (EMA) for the treatment of psoriasis, focusing on related clinical implications, also in comparison to the new generation biological therapies targeting the interleukin 23/interleukin 17 axis.Expert opinion: Pharmacodynamics of TNF α inhibitors should be fully considered in planning patient's therapy strategies, especially in case of secondary failures, poor adherence to treatment, instable psoriasis, high risk of infection, pregnant or lactating women, metabolic comorbidities, coexistence of other immune-mediated inflammatory diseases.


Assuntos
Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Antirreumáticos/farmacologia , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/farmacologia , Desenvolvimento de Medicamentos , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/farmacologia , Adesão à Medicação , Psoríase/imunologia , Psoríase/patologia , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/metabolismo
5.
Acta Gastroenterol Belg ; 82(3): 365-372, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31566323

RESUMO

BACKGROUND: The natural history of ulcerative colitis (UC) is unpredictable. Factors associated with the need for different types of step-up therapy in UC patients failing on 5-aminosalicylic acid (5-ASA) or corticosteroids are understudied. AIMS: Describe step-up therapy in patients with UC the first year after failing on 5-ASA or corticosteroids. METHODS: A Belgian, multi-center, prospective, non-interventional observational study comprising adult UC patients failing on 5-ASA or corticosteroids and naïve to immunomodulators/ biologicals. During a 12 months follow-up, patient characteristics, demography, medical therapy, biomarkers, therapy adherence and quality of life (QoL) were assessed. RESULTS: After 1 year, 35% of the patients were on biological therapy. Use of anti-TNF differed depending on baseline treatment: corticosteroid-refractory patients (55.8%), 5-ASA refractory (20.0%), and corticosteroid-dependent (16.0%) patients (p<0.001). The decision to start a line of therapy was based on the Mayo combined severity but not on biomarkers like faecal calprotectin, haemoglobin, CRP, albumin, platelets, and number of extraintestinal manifestations. At year 1, 84.2% of the patients had only mild UC or remission and a significant improvement of fatigue (p=0.004) and IBDQ scores (p<0.001) were observed implying an improved QoL. CONCLUSION: Treatment step-up, based on clinical scores in immunomodulatory and anti-TNF naïve patients with UC, provides good clinical outcomes and QoL.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Produtos Biológicos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Mesalamina/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Corticosteroides/uso terapêutico , Adulto , Nível de Saúde , Humanos , Estudos Prospectivos , Qualidade de Vida
6.
Medicine (Baltimore) ; 98(39): e17285, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574846

RESUMO

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha), among cytokines that mediate the inflammatory process, plays an important role in diseases involving the loss of intestinal barrier integrity. Several molecules with anti-TNF-alpha activity have been studied aiming to develop new therapies. The purpose of this paper is to describe the systematic review protocol of experimental studies that determine mechanisms of action of molecules with anti-TNF-alpha activity on intestinal barrier inflammation. METHODS: This protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes Protocols (PRISMA-P). The databases to be searched are PubMed, EMBASE, Scopus, ScienceDirect, and Web of Science. Experimental studies in rats or mice that assessed the activity of anti-TNF-alpha molecules in models of intestinal barrier inflammation will be included in the systematic review. Studies characteristics, experimental model, and main results will be described and the bias risk assessment will be performed. Two independent reviewers will perform study selection, data extraction, and methodological quality assessment. A narrative synthesis will be made for the included studies. Also, if sufficient data is available, a meta-analysis will be conducted. I statistics will be used to assess heterogeneity. RESULTS: The present protocol will assist in producing a systematic review that identifies the mechanisms underlying the reduction of TNF-alpha in intestinal barrier inflammation models. CONCLUSION: The systematic review may contribute to the theoretical basis of research on new molecules with anti-TNF-alpha potential and, consequently, in the development of new therapies employed in humans. PROSPERO REGISTRATION NUMBER: CRD42019131862.


Assuntos
Fármacos Gastrointestinais/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Animais , Humanos , Inflamação , Projetos de Pesquisa , Revisão Sistemática como Assunto , Fator de Necrose Tumoral alfa/antagonistas & inibidores
7.
Medicine (Baltimore) ; 98(40): e17233, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577714

RESUMO

RATIONALE: The pathology of gouty arthritis and reactive arthritis (ReA) partially overlaps, and both diseases are characterized by the production of inflammatory cytokines associated with the activation of monocytes and macrophages. However, the precise cytokine profile of cases with a coexistence of both diseases is unknown, and there are few reports on the course of treatment in patients with both gouty arthritis and ReA. PATIENT CONCERNS: A 39-year-old man with a recurrent episode of gouty arthritis presented prednisolone-resistant polyarthritis with high level of C-reactive protein (CRP). He had the features of gouty arthritis such as active synovitis of the first manifestation of metatarsophalangeal (MTP) joints and the presence of monosodium urate (MSU) crystals from synovial fluid. But he also had the features of ReA such as the presence of tenosynovitis in the upper limb, the positivity of human leukocyte antigen (HLA)-B27, a history of sexual contact and positive findings of anti-Chlamydia trachomatis-specific IgA and IgG serum antibodies. DIAGNOSES: He was diagnosed with HLA-B27 associated Chlamydia-induced ReA accompanied by gout flares. INTERVENTIONS: He was treated with 180 mg/day of loxoprofen, 1 mg/day of colchicine, and 10 mg/day of prednisolone for gout flares. However, his polyarthritis worsened with an increased level of CRP (23.16 mg/dL). Accordingly, we added 500 mg/day of salazosulfapyridine followed by adalimumab (ADA) 40 mg once every 2 weeks. OUTCOMES: After starting ADA, the patient's symptoms and laboratory findings showed rapid improvement and he achieved clinical remission 1 month after initiation of ADA treatment. As of this writing, the patient's clinical remission has been maintained for >1 year. LESSONS: This case suggests that with exacerbation of arthritis during gouty arthritis, coexistence with other pathologies such as peripheral spondyloarthritis should be considered, and early intensive treatment including tumor necrosis factor inhibitors may be necessary.


Assuntos
Artrite Reativa/etiologia , Infecções por Chlamydia/complicações , Gota/complicações , Adulto , Artrite Reativa/tratamento farmacológico , Proteína C-Reativa/análise , Infecções por Chlamydia/tratamento farmacológico , Chlamydia trachomatis , Citocinas/metabolismo , Gota/tratamento farmacológico , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Fator de Necrose Tumoral alfa/antagonistas & inibidores
8.
Praxis (Bern 1994) ; 108(12): 799-806, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31530124

RESUMO

From Axial Spondyloarthritis to Osteoporosis - Spectrum of Skeletal Involvement in Inflammatory Bowel Diseases Abstract. Inflammatory bowel diseases (IBD) are frequently accompanied by non-inflammatory joint pain and inflammatory spondyloarthritides. Spondyloarthritides can restrict joint function and typically manifest with inflammatory back pain with nightly pain and morning stiffness that improves upon exercising. In other patients, small or large peripheral joints are predominantly involved. Treatment comprises pain medication including COX-II selective non-steroidal anti-inflammatory drugs (NSAID), since non-selective NSAID can aggravate IBD. For axial manifestations, physiotherapy and tumor necrosis factor (TNF) inhibitors are effective, while for peripheral manifestations steroid injections, sulfasalazine and TNF inhibitors are useful. Osteopenia and osteoporosis may result from inflammation, malabsorption and/or steroids. Long-lasting disease activity or steroid treatment should prompt osteoporosis screening. Adequate calcium and vitamin D intake must be ensured and treatment with bisphosphonates evaluated.


Assuntos
Doenças Inflamatórias Intestinais , Osteoporose , Espondilartrite , Anti-Inflamatórios não Esteroides/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Espondilartrite/complicações , Espondilartrite/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores
9.
APMIS ; 127(12): 789-796, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31512766

RESUMO

The aim was to examine anti-tumor necrosis factor α (anti-TNFα) therapy influence changes on Th17 and Th22 cells in patients with spondyloarthritis (SpA), and its correlation with changes in clinical and magnetic resonance imaging (MRI) activity and chronicity scores. The Th17 and Th22 cells were assessed at baseline, after 12 and 52 weeks of anti-TNFα therapy by flow cytometry (ClinicalTrials.gov NCT4682724). The percentages of both Th17 and Th22 cells were increased by 70% at baseline compared with healthy controls (both p < 0.01). During treatment, these two subsets increased further to be 170% (Th17) and 123% (Th22) above levels in healthy controls (both p < 0.01). The same subsets decrease their expression of IL-23R significantly during the observation period (p < 0.05). High levels of Th17 and Th22 cells at baseline were associated with the degree of chronic changes in the sacroiliac joints on MRI and a good clinical response to anti-TNFα treatment after one year. Plasma levels were not associated with clinical changes. Th17 cells, and Th22 subsets, increased during one year of anti-TNF-α therapy in SpA, regardless of their clinical improvement. This supports that both the Th17 and Th22 subsets could be involved in the progression in SpA.


Assuntos
Anti-Inflamatórios/uso terapêutico , Espondilartrite/tratamento farmacológico , Linfócitos T Auxiliares-Indutores/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anti-Inflamatórios/farmacologia , Feminino , Citometria de Fluxo , Humanos , Interleucina-17/metabolismo , Interleucinas/metabolismo , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina/metabolismo , Espondilartrite/diagnóstico por imagem , Espondilartrite/imunologia , Espondilartrite/patologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Células Th17/metabolismo , Resultado do Tratamento
10.
Bratisl Lek Listy ; 120(8): 586-592, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379182

RESUMO

OBJECTIVE: In recent years, neutrophil-lymphocyte rate (NLR) and platelet-lymphocyte rate (PLR) are reported to be increasing in plenty of rheumatological diseases and the latter rates to be disease activity indicators. In our study, we aimed to search for the difference in NLR and PLR before and after the treatment, their relationship with the disease activity and their seasonal differences in patients using anti-TNF medication for rheumatoid arthritis (RA) and ankylosing spondylitis (AS) while. METHOD: Sixty-eight RA and 203 AS patients using anti-TNF medication for at least 6 months were included in the study. Patients with acute infection, diabetes, hypertension, cancer, renal failure and liver failure were excluded from the study. NLR, PLR, seasonal differences and the disease activities of the patients were evaluated retrospectively. RESULTS: We determined that NLR and PLR are strongly correlated with disease activity, erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP). In addition, we determined that disease activity, thrombocytes and PLR are increased in spring and winter, especially in patients with RA. CONCLUSION: NLR and PLR are simple, cheap, and easily accessible parameters which can be used to evaluate disease activity and treatment response before and after anti-TNF treatment. Further studies are needed to enlighten the effect of seasonal differences on disease activity (Tab. 2, Fig. 2, Ref. 43).


Assuntos
Artrite Reumatoide/tratamento farmacológico , Estações do Ano , Espondilite Anquilosante/tratamento farmacológico , Artrite Reumatoide/patologia , Plaquetas/citologia , Contagem de Células , Humanos , Linfócitos/citologia , Neutrófilos/citologia , Estudos Retrospectivos , Espondilite Anquilosante/patologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores
11.
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
12.
Cochrane Database Syst Rev ; 8: CD012448, 2019 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-31425625

RESUMO

BACKGROUND: Kawasaki disease (KD) is an acute inflammatory vasculitis (inflammation of the blood vessels) that mainly affects children between six months and five years of age. The vasculitis primarily impacts medium-sized blood vessels, especially in the coronary arteries. In most children, intravenous immunoglobulin (IVIG) and aspirin therapy rapidly reduce inflammatory markers, fever, and other clinical symptoms. However, approximately 15% to 20% of children receiving the initial IVIG infusion show persistent or recurrent fever and are classified as IVIG-resistant. Tumor necrosis factor-alpha (TNF-α) is an inflammatory cytokine that plays an important role in host defence against infections and in immune responses. Several studies have established that blocking TNF-α is critical for obtaining anti-inflammatory effects in children with KD, thus, there is a need to identify benefits and risks of TNF-α blockers for the treatment of KD. OBJECTIVES: To evaluate the efficacy and safety of using TNF-α blockers (i.e. infliximab and etanercept) to treat children with Kawasaki disease. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 19 September 2018. We also undertook reference checking of grey literature. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared TNF-α blockers (i.e. infliximab and etanercept) to placebo or other drugs (including retreatment with IVIG) in children with KD, reported in abstract or full-text. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the study selection criteria, assessed risk of bias and extracted data. When necessary, we contacted study authors for additional information. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included five trials from 14 reports, with a total of 494 participants. All included trials were individual RCTs that examined the effect of TNF-α blockers for KD.Five trials (with 494 participants) reported the incidence of treatment resistance. TNF-α blockers reduced the incidence of treatment resistance (TNF-α blocker intervention group 30/237, control group 58/257; risk ratio (RR) 0.57, 95% confidence interval (CI) 0.38 to 0.86; low-certainty evidence).Four trials reported the incidence of coronary artery abnormalities (CAAs). Three trials (with 270 participants) contributed data to the meta-analysis, since we could not get the data needed for the analysis from the fourth trial. There was no clear difference between groups in the incidence of CAAs (TNF-α blocker intervention group 8/125, control group 9/145; RR 1.18, 95% CI 0.45 to 3.12; low-certainty evidence).Three trials with 250 participants reported the adverse effect 'infusion reactions' after treatment initiation. The TNF-α blocker intervention decreased infusion reactions (TNF-α blocker intervention group 0/126, control group 15/124; RR 0.06, 95% CI 0.01 to 0.45; low-certainty evidence).Two trials with 227 participants reported the adverse effect 'infections' after treatment initiation. There was no clear difference between groups (TNF-α blocker intervention group 7/114, control group 10/113; RR 0.68, 95% CI 0.33 to 1.37; low-certainty evidence).One trial (with 31 participants) reported the adverse effect 'cutaneous reactions' (rash and contact dermatitis). There was no clear difference between the groups for incidence of rash (TNF-α blocker intervention group 2/16, control group 0/15; RR 4.71, 95% CI 0.24 to 90.69; very low-certainty evidence) or for incidence of contact dermatitis (TNF-α blocker intervention group 1/16, control group 3/15; RR 0.31, 95% CI 0.04 to 2.68; very low-certainty evidence).No trials reported other adverse effects such as injection site reactions, neutropenia, infections, demyelinating disease, heart failure, malignancy, and induction of autoimmunity. AUTHORS' CONCLUSIONS: We found a limited number of RCTs examining the effect of TNF-α blockers for KD. In summary, low-certainty evidence indicates that TNF-α blockers have beneficial effects on treatment resistance and the adverse effect 'infusion reaction' after treatment initiation for KD when compared with no treatment or additional treatment with IVIG. Further research will add to the evidence base. Due to the small number of underpowered trials contributing to the analyses, the results presented should be treated with caution. Further large high quality trials with timing and type of TNF-α blockers used are needed to determine the effects of TNF-α blockers for KD.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Pré-Escolar , Humanos , Fatores Imunológicos , Lactente , Ensaios Clínicos Controlados Aleatórios como Assunto , Vasculite/tratamento farmacológico
13.
Medicine (Baltimore) ; 98(33): e16622, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415355

RESUMO

OBJECTIVE: This study aimed to investigate the correlation of serum Jun-amino-terminal kinase (JNK) pathway-associated phosphatase (JKAP) level with disease risk, severity, inflammation, and treatment response to tumor necrosis factor (TNF)-α inhibitor in Crohn disease (CD) patients. METHOD: Ninety-six active CD patients and 90 healthy controls (HCs) were consecutively enrolled. Serum JKAP level of participants was determined via enzyme-linked immunosorbent assay (ELISA). In CD patients, C-reactive protein (CRP), erythrocyte sedimentation rate, Crohn disease activity index (CDAI), and inflammatory cytokine levels (determined by ELISA) were recorded. All CD patients underwent infliximab (IFX) treatment for 12 weeks, then treatment response (defined as decrement of CDAI ≥70) was assessed at week 12 (W12). RESULTS: Serum JKAP level in CD patients was lower compared to HCs, and it disclosed a good predictive value for decreased CD risk; meanwhile, it was negatively correlated with CRP level, CDAI score, TNF-α, interleukin (IL)-6, and IL-17 levels in CD patients. Sixty-eight (70.8%) patients achieved treatment response to IFX at W12, and JKAP level was increased at W12 compared to baseline. Interestingly, baseline JKAP level in response patients was decreased compared to nonresponse patients, and it exhibited a good predictive value for decreased treatment response to IFX, multivariate logistic regression revealed that JKAP was an independent factor for predicting reduced IFX response. CONCLUSION: Circulating JKAP expression correlates with decreased disease risk, activity, and inflammation level, and it could be served as a novel biomarker for predicting reduced clinical response to TNF-α inhibitor in CD patients.


Assuntos
Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Sistema de Sinalização das MAP Quinases/fisiologia , Monoéster Fosfórico Hidrolases/sangue , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Doença de Crohn/sangue , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Inflamação , Infliximab/uso terapêutico , Masculino , Fatores de Risco , Resultado do Tratamento
14.
J Drugs Dermatol ; 18(8): 776-788, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31424708

RESUMO

Psoriasis (PsO) is a common, systemic, chronic inflammatory disease characterized by key clinical symptoms, including itching, pain, and scaling, and is associated with substantial physical, psychosocial, and economic health burdens. Currently, there is no cure for PsO; however, the introduction of biologic therapies has revolutionized the clinical management of patients with PsO by expanding treatment options to include multiple therapies with different mechanisms of action targeting cytokines, including tumor necrosis factor inhibitors (TNFis), interleukin (IL)-17A inhibitors, an IL-12/23 inhibitor, and IL-23 inhibitors. TNFis are historically considered the first-line biologic treatment and the first-generation biologics; however, increased understanding of TNF-α and IL-17 synergistic functions have recently led to evidence that specifically targeting IL-17 may be more likely to improve disease activity than a more general, nonspecific therapy target, such as TNF-α. This review highlights currently available evidence and demonstrates the differences between TNFis and IL-17A inhibitors in patients with PsO with regard to efficacy and safety.


Assuntos
Produtos Biológicos/uso terapêutico , Interleucina-17/antagonistas & inibidores , Psoríase/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Produtos Biológicos/farmacologia , Ensaios Clínicos como Assunto , Humanos , Reação no Local da Injeção/epidemiologia , Reação no Local da Injeção/etiologia , Interleucina-17/imunologia , Psoríase/diagnóstico , Psoríase/imunologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/etiologia , Índice de Gravidade de Doença , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologia
15.
Z Gastroenterol ; 57(7): 843-851, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31288280

RESUMO

OBJECTIVES: This study aimed to describe biologic treatment of German inflammatory bowel disease (IBD) patients, including biologics' dosage, health care resource use, and treatment-associated cost. METHODS: In this retrospective claims data analysis, all continuously insured adult IBD patients (Crohn's disease [CD] or ulcerative colitis [UC]) who started a new therapy with an anti-tumor necrosis factor alpha (anti-TNF-α) or vedolizumab (VDZ) were included. Observation started with the date of the first prescription of index biologic therapy and lasted 12 months. RESULTS: In the database, 1248 out of 57 296 IBD patients started a biologic treatment of interest (1020 anti-TNF-α, 228 VDZ), and 837 patients were bio-naïve (773 anti-TNF-α, 64 VDZ). The mean age of bio-naïve/bio-experienced anti-TNF-α patients was 39.2/38.1 years (54.9 %/56.7 % female) and 42.6/37.8 years for VDZ patients (56.3 %/54.9 % female). The proportion of patients receiving a maintenance dosage > 150 % compared to SmPC was 15.1 % for Adalimumab, 5.2-39.0 % for Golimumab, 14.7-34.5 % for Infliximab, and 19.7 % for VDZ patients. During the maintenance phase, up to 58.8 % of patients received at least 1 prescription of any CS, and 41.7 %/47.1 % (anti-TNF-α/VDZ) were treated in a hospital due to IBD. The mean IBD-related direct health care cost per patient year was €â€Š30 246 (anti-TNF-α)/ €â€Š28 227 (VDZ) for bio-naïve patients (p = 0.288) and €â€Š34 136 (anti-TNF-α)/ €â€Š32 112 (VDZ) for bio-experienced patients (p = 0.011). CONCLUSIONS: A substantial percentage of patients receive a high biologic dosage in the maintenance phase. Despite biologic therapy, 30-40 % receive a CS therapy and/or experience at least 1 IBD-associated hospitalization within a year, possibly indicating a remaining disease activity.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Produtos Biológicos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/economia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Colite Ulcerativa/economia , Feminino , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
J Dermatol ; 46(9): 808-811, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31290564

RESUMO

Disseminated granuloma annulare (GA) is a rare granulomatous dermatitis of unknown etiology. Treatment is often challenging and lack of a uniformly effective treatment, adds to the disease morbidity. Tumor necrosis factor (TNF)-α is an important cytokine in granuloma formation and previous reports have shown improvement of disseminated GA with anti-TNF-α therapy. Nevertheless, the underlying mechanism of actions of TNF-α inhibitors in GA remains unclear. Our aim was to evaluate alterations in the inflammatory infiltrate in a patient who experienced complete clearance of GA after treatment with infliximab. A skin biopsy was obtained before and 24 weeks after treatment with infliximab 5 mg/kg at weeks 0, 2, 6, 14 and 24. Immunohistochemical stains were performed in pre- and post-treatment biopsy specimens using CD1a, CD4, CD8, CD11c, CD32, CD68, CD69, CD163, CD183 and human leukocyte antigen (HLA)-DR to characterize alterations of the infiltrates. Parallel with clinical improvement, we observed a marked decrease in myeloid (CD11c) dendritic cells, different macrophage subsets (CD68, CD32, CD163) and T cells. In addition, a marked reduction of activation markers (HLA-DR, CD69) and CD183+ (CXCR3) cells was observed in post-treatment biopsy specimens. In conclusion, the clinical improvement of disseminated GA by infliximab is paralleled by inhibition of activated myeloid dendritic cells, different macrophage subsets and type 1 T cells.


Assuntos
Células Dendríticas/efeitos dos fármacos , Fármacos Dermatológicos/farmacologia , Granuloma Anular/tratamento farmacológico , Infliximab/farmacologia , Macrófagos/efeitos dos fármacos , Idoso , Biópsia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Fármacos Dermatológicos/uso terapêutico , Granuloma Anular/imunologia , Granuloma Anular/patologia , Humanos , Infliximab/uso terapêutico , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Receptores CXCR3/imunologia , Receptores CXCR3/metabolismo , Pele/citologia , Pele/efeitos dos fármacos , Pele/patologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologia
17.
Expert Rev Clin Pharmacol ; 12(9): 885-891, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31305158

RESUMO

Introduction: Secondary loss of response to anti-tumor necrosis factor (TNF) therapy remains a challenge in the clinical management of inflammatory bowel disease (IBD) patients. A frequently observed reason for secondary loss of response to TNF blockers is inadequate drug exposure and sub-therapeutic serum drug concentrations. Areas covered: This review presents an overview of recent research on therapeutic drug monitoring (TDM)-based dosing with anti-TNF agents in IBD. The role of reactive and proactive TDM and different approaches on how to optimize anti-TNF treatment are discussed. Expert opinion: Due to variations within and between patients, the 'one size fits all' theory does not apply to all IBD patients receiving anti-TNF agents. Timing of TDM (i.e. reactive versus proactive) is a matter of debate. Both strategies might optimize anti-TNF treatment, although most trials did not show a clinical benefit compared to conventional dosing up to now. So-called dashboard systems might have an additive value in the optimization of anti-TNF treatment, since these tools enable clinicians to really personalize anti-TNF treatment.


Assuntos
Monitoramento de Medicamentos/métodos , Fármacos Gastrointestinais/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Relação Dose-Resposta a Droga , Fármacos Gastrointestinais/farmacologia , Humanos , Medicina de Precisão/métodos , Fatores de Tempo , Fator de Necrose Tumoral alfa/antagonistas & inibidores
18.
J Dermatol ; 46(9): 802-807, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31271451

RESUMO

Perifolliculitis capitis abscedens et suffodiens (PCAS) or dissecting cellulitis is a rare condition presenting deep follicular occlusions, follicular ruptures and follicular infections in the scalp area with unknown etiology, which consequently cause primary neutrophilic cicatricial alopecia by the repeated follicular inflammation. PCAS is categorized as one of the "follicular occlusion tetrad" along with hidradenitis suppurativa, acne conglobata and pilonidal cyst. In the pathogenesis of the follicular occlusion tetrad, the involvement of neutrophils and its activator tumor necrosis factor (TNF) have been discussed. Here, we report a case of PCAS that was successfully treated with adalimumab, a human anti-TNF monoclonal antibody. This is the first Asian case of PCAS that was improved by a TNF inhibitor.


Assuntos
Adalimumab/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Celulite (Flegmão)/tratamento farmacológico , Dermatoses do Couro Cabeludo/tratamento farmacológico , Dermatopatias Genéticas/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Celulite (Flegmão)/imunologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Humanos , Injeções Subcutâneas , Masculino , Dermatoses do Couro Cabeludo/imunologia , Dermatopatias Genéticas/imunologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologia , Adulto Jovem
19.
Bratisl Lek Listy ; 120(6): 417-422, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223021

RESUMO

OBJECTIVES: We aimed to investigate the effects of infliximab and HBO (hyperbaric oxygen) used alone or in combination on oxidative stress and the severity of pancreatitis in an experimental model of AP (acute pancreatitis). MATERIAL AND METHODS: A total of 60 rats were randomly divided into five groups. Group 1 underwent laparotomy; Group 2 underwent experimental AP; Group 3 was given an infliximab infusion and underwent AP; Group 4 was subjected to HBO therapy after AP; and Group 5 was given infliximab infusion before AP and subjected to HBO therapy. Serum amylase, superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPX) levels in the pancreas tissues were measured. The pancreatic tissue samples were scored. RESULTS: There were statistically significant differences in the histopathological scores and amylase levels between non-treated AP and all the three treatment groups. Group 5 had the closest histopathological scores to the sham group. MDA levels were significantly different between non-treated AP and all the three treatment groups, but the SOD levels and GPX values were not. CONCLUSIONS: Combination of HBO therapy and Infliximab showed a synergistic effect on the reduction of histopathological severity and mortality in acute pancreatitis. All treatment modalities reduced the pathological findings by decreasing lipid peroxidation and partly increasing the antioxidant capacity in early period (Tab. 1, Fig. 3, Ref. 28).


Assuntos
Oxigenação Hiperbárica , Pancreatite , Fator de Necrose Tumoral alfa , Animais , Malondialdeído , Modelos Teóricos , Estresse Oxidativo , Pâncreas , Pancreatite/tratamento farmacológico , Pancreatite/fisiopatologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores
20.
Hautarzt ; 70(12): 969-974, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31218417

RESUMO

Systemic therapy of pregnant patients with psoriasis requires special attention and has to be adapted to disease activity throughout the pregnancy. With the approval of the first tumor necrosis factor alpha inhibitors for the treatment of these patients, a new range of options has to be discussed with the women. If the inflammatory presentation of the psoriasis demands systemic therapy, the decision for treatment should be made as early as possible, preferably before the onset of pregnancy.


Assuntos
Complicações na Gravidez , Psoríase , Fator de Necrose Tumoral alfa , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Gravidez , Complicações na Gravidez/tratamento farmacológico , Psoríase/tratamento farmacológico , Encaminhamento e Consulta , Fator de Necrose Tumoral alfa/antagonistas & inibidores
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