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1.
Medicine (Baltimore) ; 99(3): e18790, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011476

RESUMO

BACKGROUND: Chordoma is a rare malignant tumor with limited treatment. Recent studies have shown that the proliferation and invasion ability of chordoma after Tumor necrosis factor alpha (TNF-α) treatment is enhanced, which may activate the gene pathway involved in the development of chordoma. This study tends to identify differentially expressed genes (DEGs) before and after treatment of TNF-α in chordoma cell line, providing a new target for future molecular therapy of chordoma. METHODS: The gene expression profile of GSE101867 was downloaded from the Gene Expression Omnibus database, and the differentially expressed genes were obtained using GEO2R. Based on the CLUEGO plugin in Cytoscape, DEGs functionality and enrichment analysis. A protein-protein interaction (PPI) network was constructed using Cytoscape based on data collected from the STRING online dataset. The Hub genes are selected from the CytoHubba, the first 20 genes that coexist with the KEGG tumor-related pathway. RESULTS: A total of 560 genes, including 304 up-regulated genes and 256 down-regulated genes, were selected as DEGs. Obviously, GO analysis shows that up-regulated and down-regulated DEGs are mainly enriched in biological processes such as synaptic tissue, cell adhesion, extracellular matrix organization and skeletal system development. DEGs are mainly enriched in tumor-associated pathways such as Pi3k-akt Signal path, Rap1 signal path. Three key genes were identified: PDGFRB, KDR, FGF2. All of these genes are involved in the tumor-associated pathways described previously. CONCLUSION: This study is helpful in understanding the molecular characteristics of chordoma development. Hub genes PDGFRB, KDR, FGF2 and pi3k-akt signaling pathway, Rap1 signaling pathway will become a new target for the future treatment of chordoma.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/metabolismo , Cordoma/tratamento farmacológico , Cordoma/metabolismo , Fator de Necrose Tumoral alfa/uso terapêutico , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Cordoma/genética , Biologia Computacional , Perfilação da Expressão Gênica , Humanos , Análise em Microsséries
2.
Internist (Berl) ; 61(3): 313-320, 2020 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-31965234

RESUMO

A 78-year-old woman with rheumatoid arthritis on TNF-α inhibitor, methotrexate and prednisolone presented with severe but unspecific symptoms such as leg weakness, shivering, bifrontal headache, nausea and staggering. The broad range of differential diagnoses lead to intricate and time-consuming diagnostic procedures. Serology, magnetic resonance imaging and microbiological investigations represent important steps to make the final diagnosis of cerebral toxoplasmosis. Both diagnostic approach and therapy require close cooperation of different disciplines. Therapies of rheumatoid arthritis as well as of toxoplasmosis are based on a long-term treatment and could be associated with numerous harmful side effects. Continuous monitoring and permanent adjustment of therapy regimes are therefore mandatory.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Encéfalo/diagnóstico por imagem , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Infecções Oportunistas/diagnóstico , Prednisolona/uso terapêutico , Toxoplasmose Cerebral/diagnóstico , Fator de Necrose Tumoral alfa/uso terapêutico , Idoso , Antirreumáticos/efeitos adversos , Encéfalo/fisiopatologia , Diagnóstico Diferencial , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/efeitos adversos , Imagem por Ressonância Magnética/métodos , Metotrexato/efeitos adversos , Prednisolona/efeitos adversos , Toxoplasmose Cerebral/diagnóstico por imagem , Toxoplasmose Cerebral/imunologia , Toxoplasmose Cerebral/patologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/efeitos adversos
3.
Clin Exp Rheumatol ; 37 Suppl 121(6): 3-17, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31856939

RESUMO

Several epidemiologic studies report on the prevalence of Behçet's syndrome (BS) and demographic and clinical findings in patients from different countries and ethnicities. Although these studies point out geographic differences in disease course, methodologic differences make it difficult to compare the results of these studies. Recent data suggest that neutrophil extracellular trap levels are elevated in patients with BS, and that it may be a potential therapeutic target for the reduction or prevention of BS-associated thrombotic risk. Details on the mode of functioning of ERAP have been delineated and further epigenetic data reported. Wall thickness of lower extremity veins is increased among BS patients without any apparent clinical involvement. Magnetic resonance (MR) venography and Doppler ultrasonography (USG) were comparable in the diagnosis of chronic deep vein thrombosis, while MR venography is more effective in detecting collateral formations. Results were also collected on some dietary and non-dietary factors in triggering oral ulcers, while smoking seems to have a protective role. With regards to the therapy, it has been demonstrated that endovascular interventions carry the risk of inducing pathergy phenomenon. Apremilast has been convincingly shown to be useful for oral ulcers of BS and classical immunosuppressives are effective as first line therapy in more than half of patients with uveitis. While infliximab and adalimumab seem to be equally effective in the treatment of refractory uveitis of BS, the combination of adalimumab and immunosuppressives appears to be superior to immunosuppressives alone for venous thrombosis of the extremities. In addition, tocilizumab might be an alternative to anti-TNF agents for patients with arterial involvement refractory to immunosuppressives. On the other hand, the place of IL-17 inhibition in the treatment of BS still remains questionable.


Assuntos
Síndrome de Behçet , Imunossupressores/uso terapêutico , Adalimumab , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Predisposição Genética para Doença , Humanos , Úlceras Orais/etiologia , Prevalência , Fator de Necrose Tumoral alfa/uso terapêutico , Uveíte/etiologia , Trombose Venosa/etiologia
4.
Arq Gastroenterol ; 56(3): 318-322, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31633732

RESUMO

BACKGROUND: The introduction of anti-TNF agents represented a landmark in the management of both Crohn's disease (CD) and ulcerative colitis (UC), with improved efficacy and safety when compared with conventional treatment. However, significant challenges still exist in Latin America to facilitate the access of biological agents for physicians and patients. OBJECTIVE: The aim of this review was to summarize current evidence on penetration of biological agents for CD and UC in Latin America. METHODS: Data are derived from a previous complete systematic review that explored different characteristics of inflammatory bowel diseases (IBD) in Latin America. The studies fully included in this previous systematic review which contained detailed descriptions of the percentage of use of biological agents in different cohorts throughout Latin American and Caribbean countries were included, and descriptive findings were compiled, describing CD and UC penetration of these drugs in different patient cohorts from different countries. RESULTS: From the 61 studies included in the original systematic review, only 19 included data of the percentage of patients treated with biological agents. Anti-TNF use in CD varied from 1.51% in Mexico up to 46.9% in Colombia, with most of the studies describing anti-TNF use in approximately 20%-40% of CD patients. On the other side, the frequency of the use of biologics was clearly lower in UC, varying from 0% in 2009 to up 16.2% in 2018, according to two different Mexican studies. Only two studies described the penetration of anti-TNF agents in IBD overall: 13.4% in a Colombian and 37.93% in a Brazilian study. No studies described percentage of use of new biologic agents (vedolizumab and ustekinumab). CONCLUSION: Penetration of anti-TNF agents in Latin America is comparable to the rest of the world in CD, but lower in UC. With the increase in the incidence and prevalence of IBD, specific strategies to increase access to anti-TNF agents in UC and new biological agents overall are warranted.


Assuntos
Doenças Inflamatórias Intestinais/tratamento farmacológico , Fator de Necrose Tumoral alfa/uso terapêutico , Terapia Biológica , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Humanos , América Latina , Revisão Sistemática como Assunto
6.
Autoimmun Rev ; 18(12): 102398, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31639514

RESUMO

The five TNF inhibitors currently approved for the treatment of RA are characterised by differences in their molecular structures, half-lives, administration routes, dosing intervals, immunogenicity, and use in women who wish to become pregnant. TNF inhibitors still represent the first biologic after conventional synthetic DMARD (csDMARD) in the majority of patients according to registry data. This was possibly because they were historically the first biological agents available (biological DMARDS with a different mechanism of action or targeted synthetic DMARDs did not become available until 2006s), and so switching from one to another was frequent in the case of an inadequate response and/or side effects. TNF inhibitors are also efficacious for other inflammatory joint and spine diseases, and have been approved for inflammatory bowel disease, uveitis and psoriasis. In addition, national registries have provided long-term safety data and demonstrated their beneficial effect on cardiovascular morbidity and mortality. However, approximately 30-40% of patients discontinue anti-TNF treatment because of primary failure, secondary loss of response, or intolerance. The options for managing anti-TNF treatment failures include switching to an alternative anti-TNF (cycling) or to another class of targeted drug with a different mechanism of action (swapping). The aim of this review is to evaluate the pros and cons of whether it is more appropriate to choose a second anti-TNF biological agents after the failure of the first or swap treatment early.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Fator de Necrose Tumoral alfa/uso terapêutico , Fatores Biológicos/uso terapêutico , Terapia Biológica/métodos , Substituição de Medicamentos , Feminino , Humanos
7.
Medicine (Baltimore) ; 98(35): e16886, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464918

RESUMO

RATIONALE: Posterior scleritis is an ocular inflammatory disorder that can be associated with both infectious and non-infectious immune reactions. Behcet disease is a chronic, relapsing, multisystemic inflammatory disorder with uveitis. There are no reported cases of posterior scleritis with Bechet disease. PATIENT CONCERNS: A 50-year-old man previously diagnosed with systemic Behcet disease presented with ocular pain and decreased vision in the left eye. DIAGNOSIS: Posterior scleritis associated with Behcet disease was diagnosed based on optical coherence tomography showing choroidal folds, as well as contrast computed tomography and ultrasound sonography demonstrating thickening of the posterior sclera. INTERVENTIONS: Treatment with systemic corticosteroids was initiated. Since inflammation relapsed during steroid tapering, anti-tumor necrosis factor-alpha (TNF-α) therapy was used in combination, and tapering of steroids was possible without recurrence of inflammation for 12 months. OUTCOMES: Posterior scleritis was resolved and visual acuity improved. With the continuation of TNF-α therapy, oral prednisolone was successfully tapered and discontinued. No relapse of inflammation was observed at follow-up 1 year after discontinuation of prednisolone. LESSONS: Ophthalmologists should be aware of the possibility of rare manifestation of posterior scleritis in patients with Behcet disease, and that combined use of systemic steroids and anti-TNF-α therapy may resolve the scleritis without recurrence of inflammation.


Assuntos
Corticosteroides/uso terapêutico , Síndrome de Behçet/complicações , Esclerite/diagnóstico por imagem , Fator de Necrose Tumoral alfa/uso terapêutico , Corticosteroides/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Esclerite/tratamento farmacológico , Esclerite/etiologia , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator de Necrose Tumoral alfa/farmacologia , Ultrassonografia , Acuidade Visual/efeitos dos fármacos
8.
Mayo Clin Proc ; 94(7): 1287-1295, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31272570

RESUMO

OBJECTIVE: To investigate an association between tumor necrosis factors-alpha (TNFα) inhibitors or other immunosuppressants and the development of uveal and cutaneous melanoma. PATIENTS AND METHODS: We performed a retrospective incidence and case-control analysis of patients in Olmsted County, MN, who were diagnosed with uveal or cutaneous melanoma from January 1, 2000, to December 31, 2014. Incidence was adjusted by age and gender to the 2010 US white population. Controls were matched by sex and age to cases at time of diagnosis of melanoma. RESULTS: There were 1221 cases of melanoma (33 uveal, 1188 cutaneous). Combined incidence of uveal and cutaneous melanoma per 100,000 person-years varied by gender (male > female), age (older > younger), and time period: 2010 to 2014 (77.9, 95% confidence interval [CI], 71.1-84.7) ≈ 2005 to 2009 (78.0, 95% CI, 70.9-85.0) > 2000 to 2004 (42.5, 95% CI, 36.9-48.1, P<.001). TNFa inhibitor prescription was not associated with significantly increased risk of melanoma vs controls (1.06% vs 0.41%, P=.06). Immunosuppressive agents, high-dose corticosteroids, and topical immunosuppressants were associated with melanoma (odds ratio [OR] 1.42 CI, 1.03-1.95, 3.30 CI, 2.44-4.48, and 1.87 CI, 1.06-3.28, respectively). An increased number of patients with uveal melanoma received immune modulating agents vs controls, but this was not statistically significant (P=.36). Autoimmune disease itself was not correlated with melanoma (P=.73). CONCLUSION: Exposure to immunosuppressive agents is associated with melanoma. TNFa inhibition and autoimmune disease alone do not significantly increase risk of melanoma. In patients receiving immunosuppressive treatments, physicians should consider monitoring with dilated ophthalmic and full-body skin examinations. Further studies are needed to assess the impact of TNFa inhibitors on development of melanoma, particularly in uveal melanoma.


Assuntos
Imunossupressores/efeitos adversos , Melanoma/induzido quimicamente , Neoplasias Cutâneas/induzido quimicamente , Fator de Necrose Tumoral alfa/efeitos adversos , Neoplasias Uveais/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Masculino , Melanoma/epidemiologia , Melanoma/patologia , Pessoa de Meia-Idade , Minnesota/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/uso terapêutico , Neoplasias Uveais/epidemiologia , Neoplasias Uveais/patologia
9.
Medicine (Baltimore) ; 98(26): e15947, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261500

RESUMO

To assess the hypothesis if tocilizumab (TCZ) is effective on disease activity, and also its effect in fatigue and other clinical and psychological disease-related factors in patients with rheumatoid arthritis (RA) treated with TCZ.A 24-week, multicenter, prospective, observational study in patients with moderate to severe RA receiving TCZ after failure or intolerance to disease-modifying antirheumatic drugs or tumor necrosis factor-alpha was conducted.Of the 122 patients included, 85 were evaluable for effectiveness (85% female, 51.9 ±â€Š12.5 years, disease duration 8.7 ±â€Š7.4 years). Mean change in C-reactive protein level from baseline to week 12 was -11.2 ±â€Š4.0 (P < .001). Mean Disease Activity Index score (DAS28) decreased from 5.5 ±â€Š1.0 at baseline to 2.7 ±â€Š1.3 (P < .001) at week 24. Mean change in Functional Assessment of Chronic Illness Therapy score was -5.4 ±â€Š11.2 points at week 24. Multiple regression analysis showed that the improvement in DAS28, sleep, and depression explained 56% and 47% of fatigue variance at week 12 and 24, respectively.Tocilizumab is effective in reducing disease activity and results in a clinically significant improvement in fatigue, pain, swollen joint count, morning stiffness, sleepiness, depression, and DAS28; the last 3 were specifically identified as factors explaining fatigue variance with the use of TCZ in RA patients.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/psicologia , Artrite Reumatoide/terapia , Fadiga/psicologia , Fadiga/terapia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/fisiopatologia , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Depressão/fisiopatologia , Depressão/terapia , Fadiga/etiologia , Fadiga/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Retratamento , Sono , Resultado do Tratamento , Fator de Necrose Tumoral alfa/uso terapêutico
10.
Acta Gastroenterol Belg ; 82(2): 326-328, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31314197

RESUMO

In this case report we describe the evolution of Cheilitis granulomatosa (GC) in a young patient with Crohn's disease during treatment with anti-TNF-alfa therapy.


Assuntos
Doença de Crohn/diagnóstico , Imunossupressores/uso terapêutico , Imunoterapia , Síndrome de Melkersson-Rosenthal/etiologia , Fator de Necrose Tumoral alfa/uso terapêutico , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Humanos , Resultado do Tratamento
12.
Int J Technol Assess Health Care ; 35(4): 266-272, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31337453

RESUMO

OBJECTIVES: As more health technology assessment (HTA) bodies seek to implement patient involvement, there is a desire to learn from other HTA bodies about their experiences and understand what approaches can be used and which ones make a real difference to HTA. This is difficult, as the impact of patient involvement in HTA is not well documented. This study aims to promote further discussion about the ways in which patient involvement can impact HTAs by studying stories of impact. METHODS: In a multi-stakeholder workshop, experts leading patient involvement in four HTA bodies shared examples of HTAs where they believed patient involvement made a difference, then they reflected on these impact stories within the wider context of impact evaluation. RESULTS: The HTA bodies drew on patient input and patient-based evidence to inform their HTAs. The patient involvement was observed to elucidate patients' experiences, needs and preferences which, in turn, was observed to influence the HTA recommendations about optimal use of technologies, including taking account of issues for sub-groups, outcomes that matter to patients and educational needs. CONCLUSIONS: Personal stories of patient involvement may enable a wider understanding of different approaches to and impact of patient involvement. The examples relate to both patient input and patient-based evidence and highlight the role that patient involvement can play in reducing uncertainties and complementing the clinical and economic evidence in HTA. They suggest that impact can be seen in recommendations about how and when a technology is used.


Assuntos
Prática Clínica Baseada em Evidências/organização & administração , Participação do Paciente/métodos , Avaliação da Tecnologia Biomédica/organização & administração , Bandagens/normas , Humanos , Apneia Obstrutiva do Sono/terapia , Avaliação da Tecnologia Biomédica/normas , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/uso terapêutico
13.
Platelets ; 30(8): 1047-1052, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31076004

RESUMO

Increased reactive oxygen species (ROS) production leads to tissue damage observed in sepsis and lipopolysaccharide (LPS)-exposed animals. LPS stimulates cytokines releasing, including tumor necrosis factor alpha (TNF-α), that is important to ROS production. Platelets, considered inflammatory cells, generate ROS when exposed to LPS in vivo, but not when they are incubated in vitro with this compound. Therefore, we investigated the role of TNF-α on the increased intraplatelet ROS levels after LPS treatment. Mice were injected with LPS (1 mg/kg) or TNF-α (10 ng/kg), and blood was collected to prepare the washed platelets. Animals were treated with infliximab (anti-TNF-α antibody), R-7050 (non-selective TNF-α receptor antagonist) or apocynin (NADPH oxidase inhibitor). At 48 h after LPS or TNF-α injection, the ROS levels in ADP (25 µM)-activated platelets were evaluated by flow cytometry. Our data showed that injection of mice with LPS increased by 4-fold the ROS production (p < 0.05), which was significantly reduced by the treatments with infliximab, R-7050 or apocynin. Injection of mice with TNF-α markedly elevated the ROS formation in platelets (p < 0.05) that was reduced by infliximab, R-7050 or apocynin treatments. In separate experiments, platelets from saline-injected mice were incubated with TNF-α (30 to 3000 pg/mL) in absence or presence of infliximab, R-7050, apocynin or GKT137831 (NOX1/NOX4 inhibitor) before ROS measurements. TNF-α in vitro markedly increased the ROS levels, an effect significantly reduced by all treatments. Therefore, platelets are involved in the oxidative stress induced by LPS through TNF-α action, and NADPH oxidase takes part in this effect.


Assuntos
Plaquetas/metabolismo , Lipopolissacarídeos/metabolismo , Fator de Necrose Tumoral alfa/uso terapêutico , Animais , Humanos , Masculino , Camundongos , Espécies Reativas de Oxigênio , Fator de Necrose Tumoral alfa/farmacologia
14.
Clin Exp Rheumatol ; 37(4): 680-683, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943133

RESUMO

OBJECTIVES: The aim of the study was to evaluate the efficacy of golimumab (GOL) and certolizumab pegol (CZP) as additional treatment options for the treatment of uveitis. METHODS: Patients with longstanding uveitis receiving either GOL or CZP were retrospectively evaluated in terms of frequency of ocular flares, drug survival, changes in best corrected visual acuity (BCVA) and steroid-sparing effect. RESULTS: Twenty-one patients (30 eyes), 17 of whom being female, were enrolled in the study; 16 out of 21 patients had been previously treated with other tumour necrosis factor (TNF)-α blockers. A significant reduction in ocular flares (from 128.6 bouts for 100 patients-year to 42.9 events for 100 patients-year) was observed between the 12 months prior to the start of GOL or CZP and the 12 months thereafter (p=0.01). The 36-month drug survival was 54.5% for CZP and 50.0% for GOL with no statistically significant differences between the two biologic agents. No differences were detected concerning BCVA values and the mean corticosteroid intake between baseline and the last follow-up. The safety profile was excellent. CONCLUSIONS: GOL and CZP represent effective and safe treatment choices for patients with uveitis also when unsuccessfully treated with other anti-TNF-α drugs, permitting a significant reduction in the frequency of ocular flares and preserving visual function with a good long-term retention rate.


Assuntos
Fator de Necrose Tumoral alfa , Uveíte/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Certolizumab Pegol/efeitos da radiação , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/uso terapêutico
15.
Autoimmun Rev ; 18(5): 439-454, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30844556

RESUMO

Ulcerative colitis (UC) and Crohn's disease (CD) are the two major types of inflammatory bowel disease (IBD). We conducted a comprehensive review of meta-analyses to summarize the reported effectiveness of different drugs for IBD. We performed a literature search and a total of 110 meta-analyses from 66 articles were summarized and re-analyzed (62 in UC and 48 in CD). In summary, 5-ASA was more effective than placebo in both induction and maintenance treatment of UC, but there were conflicting results on the effect of 5-ASA on the induction treatment or relapse of CD. The use of immunomodulatory agents in the induction or maintenance phase of UC and CD using immunomodulators appeared to be more effective than placebo, but the results were impacted by small number of patients, discordant results with the largest study and risk of biases. Anti-TNF-α and anti-integrin therapeutic antibodies in both, induction and maintenance, showed a better efficacy than placebo in a large proportion of patients analyzed. Other agents, such as probiotics, antibiotics, omega-3, were shown to be more effective than placebo, but the same issues arose as stated above with the use of immunomodulatory agents. In conclusion, we performed a comprehensive review of meta-analysis on comparative efficacy of pharmacotherapy used in the management of IBD. Our review will augment our understanding of the treatment of UC and CD by providing a guideline for interpreting the statistically significant findings and discusses the optimal choice for IBD treatment.


Assuntos
Quimioterapia de Indução/métodos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Quimioterapia de Manutenção/métodos , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Humanos , Doenças Inflamatórias Intestinais/patologia , Probióticos/uso terapêutico , Recidiva , Indução de Remissão , Fator de Necrose Tumoral alfa/uso terapêutico
16.
Intern Med ; 58(12): 1703-1712, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30799358

RESUMO

Objective Biological disease-modifying anti-rheumatic drugs (bDMARDs) represent an important advance in alleviating rheumatoid arthritis (RA), but their effect on rheumatic airway disease (AD) and interstitial lung disease (ILD) is still unclear. This study was performed to evaluate the association of the use of different bDMARDs with new-onset or worsening of RA-AD/ILD. Methods We performed a retrospective cohort study of RA patients who received bDMARDs and assessed their AD/ILD before and after drug initiation in our hospital over the past 10 years. We evaluated the serial changes in computed tomography (CT), classified patients according to AD/ILD progression, and analyzed associations between clinical characteristics and outcomes. Results We enrolled 49 patients. Thirty patients received tumor necrosis factor inhibitors (TNFis), 12 received abatacept (ABT), and the remaining 7 received tocilizumab (TCZ). Seventeen patients had ILD, 10 had AD, and 6 had both AD and ILD before the initiation of bDMARDs. New emergence or exacerbation of AD/ILD was observed in 18 patients after drug initiation, while the remaining 31 remained stable or improved. Multiple logistic regression analyses revealed that pre-existing AD was an independent risk factor against the emergence or exacerbation of RA-AD/ILD, and ABT use was a protective factor against it. Conclusion Our study showed that pre-existing RA-AD is associated with future worsening of RA-AD/ILD, and ABT over other bDMARDs was associated with a better prognosis. Future studies to confirm our results are needed.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Abatacepte/uso terapêutico , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Artrite Reumatoide/fisiopatologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Fator de Necrose Tumoral alfa/uso terapêutico
17.
World J Microbiol Biotechnol ; 35(3): 45, 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30810891

RESUMO

Dysbiosis of intestinal microbiota and aberrant inflammatory responses in gastrointestinal mucosa plays important roles in the development of inflammatory bowel disease (IBD). The purpose of this study was to demonstrate the probiotic activity of Lactococcus lactis and the ability of TNF-α-binding by recombinant L. lactis bearing TNF-α-binding affibodies. Various concentrations of recombinant L. lactis were exposed to TNF-α and its binding measured by ELISA. Mucosal biopsies of patients with active IBD were incubated with various L. lactis strains or E. coli DH5α strain and concentrations of TNF-α, IL-23, and IL-10 in the supernatants determined by ELISA. Recombinant L. lactis, at 1 × 109 and 1 × 108 CFU/mL, bound 22.6% and 18.4%, respectively of TNF-α (p < 0.05). When IBD-mucosa was incubated with any L. lactis strain at 1 × 109 CFU/mL, levels of TNF-α and IL-23 were significantly decreased and that of IL-10 increased relative to that for the sterile culture. Opposite trends were observed with E. coli cultures. Recombinant L. lactis at 1 × 108 CFU/mL bound as much as 62.8% (p = 0.026) of TNF-α in IBD-mucosa supernatants compared with the control strain. L. lactis strains are reported, for the first time, to induce an ex vivo anti-inflammatory cytokine profile in IBD inflamed mucosa. L. lactis could therefore constitute a promising alternative approach for treating IBD.


Assuntos
Anti-Inflamatórios/metabolismo , Citocinas/metabolismo , Engenharia Genética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mucosa Intestinal/microbiologia , Lactococcus lactis/genética , Lactococcus lactis/metabolismo , Probióticos/farmacologia , Adolescente , Anti-Inflamatórios/uso terapêutico , Criança , Citocinas/genética , Citocinas/uso terapêutico , Disbiose , Escherichia coli/genética , Escherichia coli/metabolismo , Feminino , Microbioma Gastrointestinal , Humanos , Doenças Inflamatórias Intestinais/microbiologia , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-23/genética , Interleucina-23/metabolismo , Masculino , Proteínas Recombinantes/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/uso terapêutico , Adulto Jovem
18.
Medicine (Baltimore) ; 98(5): e14181, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30702571

RESUMO

We determined whether rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) can predict remission or severe disability in rheumatoid arthritis (RA) patients treated with anti-tumor necrosis factor (TNF) alpha drugs.We performed a cohort study based on the clinical data from a referral center for the treatment of RA in Bogotá, Colombia, were included patients aged ≥18 years with diagnosis of RA with an active disease and for whom a treatment scheme was begun with anti-TNF alpha medication, with a minimum follow-up time of 12 months. Disease activity of Rheumatoid Arthritis was assessed through measurement of RF, ACPA, disease activity score (DAS28), and health assessment questionnaire (HAQ). We calculated the incidence rates (IRs) for remission and severe disability. We also calculated the incidence rate ratio (IRR) for each outcome by adjusting for possible confounders using the Poisson regression method. The hypothesis was tested with a P value of <.05. Statistical analysis was performed in Stata 15.We included 400 patients receiving an anti-TNF alpha agent. Median age was 60 years, and 322 patients were women (80.5%). RF was positive in 357 patients (89%), ACPA in 348 patients (87%), and co-positivity in 324 patients (81%). Median follow-up was 41 months (range, 12-79 months). The IR for remission was 23 per 100 person-years in RF-negative patients and 16 per 100 person-years in RF-positive patients. The adjusted IRR (age sex, treatment, and ACPA) was 1.51 (95%CI, 1.05-2.18). The IR for severe disability was 10.8 per 100 person-years in the RF-positive cohort and 2.3 per 100 person-years in the RF-negative cohort. The IRR adjusted for these factors was 4.37 (95%CI, 1.6-12). Co-positivity had a similar behavior to RF. No differences were recorded in the rates of remission or disability in ACPA-positive and ACPA-negative patients.Our findings suggest that remission is less frequent and severe disability more frequent in RF-positive patients treated with anti-TNF alpha agents than in RF-negative patients.


Assuntos
Anticorpos Anti-Proteína Citrulinada/sangue , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Fator Reumatoide/sangue , Fator de Necrose Tumoral alfa/uso terapêutico , Idoso , Anticorpos Anti-Proteína Citrulinada/biossíntese , Artrite Reumatoide/fisiopatologia , Biomarcadores , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Fator Reumatoide/biossíntese , Índice de Gravidade de Doença
19.
Clin Exp Rheumatol ; 37(4): 649-655, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30767865

RESUMO

OBJECTIVES: To determine the incidence of serious infections (SIs) among the spondyloarthropathy (SpA) patients from the "Gruppo Italiano per lo Studio delle Early Arthritis" (GISEA) registry and treated with tumour necrosis factor (TNF) inhibitors (TNFIs), and to identify the factors associated with the development of the infections. METHODS: This observational study on 3321 GISEA-registered SpA patients collected real-world demographic and clinical data relating to their biological drug treatments. The overall incidence of infections was analysed by type of SpA. RESULTS: A total of 3321 SpA patients (1731 males, 52.2%; mean age 47±13 years; median disease duration 3 years, interquartile range [IQR] 0-8) were eligible for inclusion in the analysis. Two hundred and fifty-nine patients experienced at least one of 391 microbiologically diagnosed SIs, 32% of which were recorded during the first 12 months of treatment. The overall incidence of SIs was 43.9/1000 patient-years of follow-up (95% confidence interval [CI] 39.6-48.4): 29.9/1000 (95% CI 23.1-38.1) among those treated with adalimumab (ADA); 36.1/1000 (95% CI 30.0-43.1) among those treated with etanercept (ETN); and 61.4/1000 (95% CI 53.3-70.5) among those treated with infliximab (INF). The highest incidence was observed among the patients with psoriatic arthritis (PsA), but the difference was statistically significant only in comparison with the patients with undifferentiated SpA (p=0.002), whose incidence of SIs was also lower than in the patients with ankylosing spondylitis (AS) (p=0.034). Multivariate models showed that the number of comorbidities (hazard ratio [HR] 1.29, 95%CI 1.2-1.4; p<0.001), age at the start of TNFi treatment (HR 0.99, 95%CI 0.97-0.99; p=0.030), steroid use (HR 1.40, 95%CI 1.1-1.8; p=0.012) and male sex (HR 0.72, 95%CI 0.5-0.9; p=0.012) were all statistically significant predictors of infection. The factors independently associated with a lower risk of SIs were the use of ETN (HR 0.52, 95%CI 0.4-0.7; p<0.001) or ADA (HR 0.59, 95%CI 0.4-0.8; p=0.002) rather than INF. CONCLUSIONS: The incidence of SIs was higher among patients with PsA or AS than among those with undifferentiated SpA, and among patients treated with INF than among those treated with ADA or ETN. Male sex, steroid use and the number of comorbidities were all factors predictive of SIs.


Assuntos
Antirreumáticos/efeitos adversos , Espondiloartropatias/complicações , Fator de Necrose Tumoral alfa/efeitos adversos , Adalimumab , Adulto , Antirreumáticos/uso terapêutico , Etanercepte , Feminino , Humanos , Infliximab , Itália , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Espondiloartropatias/tratamento farmacológico , Espondiloartropatias/imunologia , Inquéritos e Questionários , Fator de Necrose Tumoral alfa/uso terapêutico
20.
J Clin Pharm Ther ; 44(4): 553-560, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30763469

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Anti-tumour necrosis factor-alpha (anti-TNF-α) therapy is known to raise the risk of granulomatous infections, leading to development of risk management strategies at national or global level. This study aimed to determine the relative risk (RR) of tuberculosis (TB) due to anti-TNF-α usage in patients with rheumatologic diseases (RDs) in a nationwide basis. METHOD: This retrospective cohort study included patients with rheumatoid arthritis (RA), ankylosing spondylitis, juvenile idiopathic arthritis or psoriatic arthritis (PsA) that treated with or without anti-TNF-α agents, as registered in the national prescription information system between years 2013 and 2015. Two-year RR of TB after anti-TNF-α therapy initiation was calculated in this RD population, including main subgroups. RESULTS AND DISCUSSION: The study cohort included 413 500 RD patients, where anti-TNF-α(+) arm (n = 2117) had mean age of 41.9 ± 13.4 years and male distribution of 54.3%. Four patients among anti-TNF-α users developed TB compared to 128 patients in anti-TNF-α-naïve group (189 vs 31 cases per 100 000 patients, respectively), yielding a 2-year RR of 6.07 (95% CI, 2.25-16.42) with an attributable risk of 0.16%. These RRs (95% CI), which were particularly pronounced, were 5.39 (1.69-7.17) in men, 6.12 (2.26-16.55) in adults, and 5.70 (1.41-23.08) in RA and 13.46 (1.58-114.40) in PsA patients. There was no difference between the anti-TNF-α users who developed and undeveloped TB regarding drug utilization characteristics, except significantly less immunosuppressive drug exposure in TB patients. WHAT IS NEW AND CONCLUSION: This study is the first prescription-based nationwide study to suggest an elevated RR of TB in a comparably younger population with a broad spectrum of RDs managed with any approved anti-TNF-α drug in Turkey.


Assuntos
Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , Tuberculose/induzido quimicamente , Fator de Necrose Tumoral alfa/efeitos adversos , Fator de Necrose Tumoral alfa/uso terapêutico , Adulto , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Turquia
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