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OBJECTIVE: To present the characteristics of patients with potential difficult-to-treat (D2T) PsA. METHODS: We used data from the Greek multicentre registry of PsA patients. D2T PsA was defined as follows: patients with at least 6 months' disease duration, who have failed to at least one conventional synthetic DMARD and at least two biologic DMARDs/targeted synthetic DMARDs with a different mechanism of action and have either at least moderate disease activity (MODA) defined as DAPSA (Disease Activity index in PSoriatic Arthritis) >14, and/or are not at minimal disease activity (MDA). Demographic and clinical characteristics were compared between D2T and non-D2T PsA patients. In two sensitivity analyses, patients classified as D2T solely according to the MODA or MDA criterion were examined separately. RESULTS: Among 467 patients included, 77 (16.5%) were considered D2T and 390 non-D2T PsA. Compared with non-D2T, patients with D2T PsA presented more commonly with extensive psoriasis (P < 0.0001) and were more likely to have higher BMI (P = 0.023) and a history of IBD (P = 0.026). In the MODA and MDA sensitivity analyses, 7.5% and 12.5% of patients were considered D2T, respectively. In both sensitivity analyses, extensive psoriasis was again identified as an independent variable for D2T PsA (P = 0.001 and P = 0.008, respectively). Moreover, female gender (P = 0.034) in the MODA analysis and axial disease (P = 0.040) in the MDA analysis were independent variables for D2T PsA. CONCLUSION: Despite the availability of therapies, D2T PsA is common in real-life cohorts of patients with PsA and extensive psoriasis. High BMI, female gender, axial disease and history of IBD were also associated with D2T PsA.
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Antirreumáticos , Artrite Psoriásica , Sistema de Registros , Humanos , Artrite Psoriásica/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Antirreumáticos/uso terapêutico , Grécia/epidemiologia , Índice de Gravidade de Doença , Adulto , Produtos Biológicos/uso terapêutico , IdosoRESUMO
Background: Despite the development of treatments targeting T cell co-stimulation and cytokines TNF, IL-12/23, and IL-17, less than half of patients within clinical trials achieve high levels of clinical response. This fact, as well as the absence of prognostic biomarkers represents major unmet clinical needs that necessitate further investigation of the disease pathophysiology. Myeloid cells are critical components of PsA inflammatory mechanisms, being a highly prevalent immune population in biopsies of PsA target tissues, such as the skin and the synovium. Through their antigen-presenting capacity and their pro-angiogenic and pro-inflammatory properties myeloid cells could contribute to persistent inflammation in PsA leading to treatment-resistant disease. To this end, we have recently shown the expansion of monocytes in the blood of PsA patients compared to healthy subjects. Importantly, we have also identified an immature myeloid cell population in patients with highly active, refractory disease, indicating the presence of an "emergency myelopoiesis" process in PsA. Aim of the study: In this research protocol, we aim to decipher the pro-inflammatory "myeloid signature" in patients with active PsA and explore the role of immature myeloid cells in disease pathophysiology and their potential as prognostic biomarkers. Methods: To address this, we will isolate and analyse monocytes and immature myeloid cells from PsA patients -before and after a 6-month treatment course- focusing on differences between responders and non-responders. In this context, we will perform a thorough phenotypic and functional analysis of these cells, identify their expression signature in an already established whole blood RNA-seq dataset and investigate their presence in target tissues, such as the skin and synovial fluid. Anticipated benefits: This study will elucidate the role of myeloid cells in disease propagation by further defining the involvement of immature myeloid cells in PsA.
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To evaluate the effect of the phosphodiesterase 4 inhibitor apremilast in biologic-naïve patients with early peripheral PsA in terms of disease activity, clinical manifestations, patient-perceived outcomes, as well as apremilast's safety profile in routine care settings of Greece. Non-interventional, multicenter, 52-week prospective cohort study, enrolling biologic-naïve patients with early active peripheral PsA who started apremilast after intolerance or inadequate response (within the first 12 months of treatment) to an initial conventional synthetic (cs)DMARD treatment. Non-responder imputation was applied for missing data.In total, 167 consecutive patients (mean age: 52.5 years; median PsA duration: 0.9 years) were analyzed. At baseline, the median (interquartile range) clinical Disease Activity in Psoriatic Arthritis (cDAPSA) score was 22.0 (16.0-29.0), with 86.8% of patients having at least moderate (29.3% high) disease activity; 87.4% had skin psoriasis, 37.7% nail psoriasis, 30.7% enthesitis, and 12.4% dactylitis. At 16, 24, and 52 weeks, 28.7, 42.5, and 48.5% of patients, achieved ≥ 50% improvement in their baseline cDAPSA score, respectively. At week 52, 55.6, 50, and 26.8% of evaluable patients achieved complete resolution of enthesitis, dactylitis and nail psoriasis, respectively. Improvements were also observed in patient's health state assessed by the Psoriatic Arthritis Impact of Disease 12-item questionnaire, and health-related quality of life. The 52-week drug survival rate was 75%, while 13.8% of patients experienced at least one adverse drug reaction.Biologic-naïve patients with early PsA, treated with apremilast experienced significant improvements in disease activity, extra-articular manifestations and patient-centered outcomes, accompanied by a favorable tolerability profile.
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Anti-Inflamatórios não Esteroides , Artrite Psoriásica , Produtos Biológicos , Psoríase , Humanos , Pessoa de Meia-Idade , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Entesopatia , Estudos Prospectivos , Psoríase/tratamento farmacológico , Qualidade de VidaRESUMO
Background: Psoriatic arthritis (PsA) is a heterogenous chronic inflammatory disease affecting skin, joints, entheses, and spine with various extra-musculoskeletal manifestations and comorbidities. The reported patient, disease and treatment characteristics in the modern therapeutic era are limited. Methods: In this cross-sectional, multi-centre, nationwide study, we recorded the demographic, clinical, and therapeutic characteristics as well as the comorbidities of patients with PsA seen for 1 year (1/1/2022-31/12/2022). Results: 923 patients (55% females) with a median (IQR) age of 57 (48-65) years and a mean disease duration of 9.5 years were enrolled. Family history of psoriasis and PsA was noted in 28.3% and 6.3%, respectively. Most patients had limited psoriasis (BSA<3: 83%) while enthesitis, dactylitis, nail and axial involvement reported in 48.3%, 33.2%, 43% and 25.9% of patients, respectively. Regarding comorbidities, approximately half of patients had dyslipidaemia (42%) or hypertension (45.4%), 36.8% were obese and 17% had diabetes while 22.7% had a depressive disorder. Overall, 60.1% received biologics and among them more patients treated with anti-IL-17 or -12/23 agents were on monotherapy (64.2%) compared to those on TNFi monotherapy (49.4%, p=0.0001). The median PsA activity as assessed by the DAPSA score was 6 (IQR: 2.3 - 13.1) with 46% of patients reaching minimal disease activity status (MDA). Conclusion: In this large, real life, modern cohort of patients with PsA with frequent comorbidities who were treated mainly with biologics, almost half achieved minimal disease activity. These results show the value of existing therapeutic approaches while at the same time highlight the existing unmet needs.
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BACKGROUND: Accumulating evidence supports the role of monocytes and neutrophils in radiographic axSpA (r-axSpA). Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a growth factor for both leukocyte lineages and a pro-inflammatory cytokine activating myeloid cells and promoting osteoclastogenesis. It acts through the JAK-STAT pathway. We measured serum GM-CSF and markers of bone metabolism in patients with r-axSpA before and after anti-TNF treatment. METHODS: Patients with active r-axSpA despite treatment with NSAIDs, all eligible for treatment with a biologic agent, were recruited. Healthy donors were sampled as controls. Serum was collected before (baseline) and after 4-6 months (follow-up) of anti-TNF treatment and the following molecules were measured with ELISA: GM-CSF, sclerostin (SOST), and dickkopf-1 (Dkk-1). RESULTS: Twelve r-axSpA patients (7 males, 5 females, median age 37 years) with a median disease duration of 1 year and 16 age- and sex-matched controls were included. At baseline, patients had mean BASDAI 6.3±2 and ASDAS 3.2±0.7, which decreased to 4.1±1.7 and 2.2±0.6 at follow-up, respectively. At baseline, r-axSpA patients had significantly higher mean serum levels of GM-CSF (150 vs 62pg/ml, p=0.049), significantly lower Dkk-1 (1228 vs 3052pg/ml, p=0.001), but similar levels of SOST (369 vs 544pg/ml, p=0.144) compared to controls. Anti-TNF treatment did not affect GM-CSF, Dkk-1, or SOST levels. Spearman correlation analysis showed that GM-CSF correlated positively with ASDAS at baseline (r=0.61, p=0.039), while no correlations were identified between bone markers (Dkk-1, SOST) on one hand and GM-CSF or disease activity indices on the other. CONCLUSIONS: GM-CSF is increased in patients with active AS and strongly correlates with disease activity. TNF inhibition does not affect GM-SCF levels, despite improving disease activity. GM-CSF may represent an important pathway responsible for residual inflammation during TNF blockade, but also a potential target of JAK inhibitors, explaining their efficacy in r-axSpA.
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Espondiloartrite Axial , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Inibidores do Fator de Necrose Tumoral , Adulto , Espondiloartrite Axial/sangue , Espondiloartrite Axial/tratamento farmacológico , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Humanos , Janus Quinases , Masculino , Fatores de Transcrição STAT , Transdução de Sinais , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
The co-existence of an autoinflammatory syndrome with a demyelinating disorder is a very rare occurrence raising the question whether there is a pathophysiological connection between them. We describe the case of a man with symptoms of cryopyrin-associated periodic syndrome (CAPS) since infancy who later developed multiple sclerosis (MS). As CAPS was genetically confirmed, the inhibition of interleukin-1 (IL-1) with anakinra led to a swift resolution of the CAPS symptoms and also, in combination with teriflunomide, to a clinical and imaging improvement of MS. In vitro studies showed that, upon a CAPS flare, the patient's peripheral neutrophils released neutrophil extracellular traps (NETs) decorated with IL-1ß, while NET release was markedly decreased following anakinra-induced remission of CAPS. Taking into account the growing evidence on the involvement of IL-1ß in experimental models of MS, this rare patient case suggests that the role of neutrophils/NETs and IL-1ß in MS should be further studied.
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Síndromes Periódicas Associadas à Criopirina/imunologia , Armadilhas Extracelulares/imunologia , Interleucina-1beta/imunologia , Esclerose Múltipla/imunologia , Neutrófilos/imunologia , Adulto , Antirreumáticos/uso terapêutico , Encéfalo/diagnóstico por imagem , Crotonatos/uso terapêutico , Síndromes Periódicas Associadas à Criopirina/complicações , Síndromes Periódicas Associadas à Criopirina/tratamento farmacológico , Síndromes Periódicas Associadas à Criopirina/fisiopatologia , Humanos , Hidroxibutiratos/uso terapêutico , Imunossupressores/uso terapêutico , Técnicas In Vitro , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/tratamento farmacológico , Nitrilas/uso terapêutico , Toluidinas/uso terapêuticoRESUMO
This is a case report describing a patient with severe thyroid eye disease complicated with dysthyroid optic neuropathy that was unresponsive to intravenous steroids and orbital radiotherapy but responded well to intravenous tocilizumab.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Oftalmopatia de Graves/tratamento farmacológico , Doenças do Nervo Óptico/tratamento farmacológico , Oftalmopatia de Graves/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Nervo Óptico/radioterapia , Esteroides/administração & dosagem , TireoidectomiaRESUMO
Ankylosing spondylitis (AS) is an inflammatory disease characterized by excessive bone formation. We investigated the presence of neutrophil extracellular traps (NETs) in AS and how they are involved in the osteogenic capacity of bone marrow mesenchymal stem cells (MSCs) through interleukin-17A (IL-17A). Peripheral neutrophils and sera were obtained from patients with active AS and healthy controls. NET formation and neutrophil/NET-associated proteins were studied using immunofluorescence, immunoblotting, qPCR, and ELISA. In vitro co-culture systems of AS NET structures and MSCs isolated from controls were deployed to examine the role of NETs in the differentiation of MSCs toward osteogenic cells. Analysis was performed using specific staining and qPCR. Neutrophils from patients with AS were characterized by enhanced formation of NETs carrying bioactive IL-17A and IL-1ß. IL-17A-enriched AS NETs mediated the differentiation of MSCs toward bone-forming cells. The neutrophil expression of IL-17A was positively regulated by IL-1ß. Blocking IL-1ß signaling on neutrophils with anakinra or dismantling NETs using DNase-I disrupted osteogenesis driven by IL-17A-bearing NETs. These findings propose a novel role of neutrophils in AS-related inflammation, linking IL-17A-decorated NETs with the differentiation of MSCs toward bone-forming cells. Moreover, IL-1ß triggers the expression of IL-17A on NETs offering an additional therapeutic target in AS.
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Diferenciação Celular/imunologia , Armadilhas Extracelulares/imunologia , Interleucina-17/imunologia , Células-Tronco Mesenquimais/imunologia , Osteogênese/imunologia , Adulto , Diferenciação Celular/genética , Células Cultivadas , Armadilhas Extracelulares/metabolismo , Feminino , Humanos , Interleucina-17/genética , Interleucina-17/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Neutrófilos/citologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Osteogênese/genética , Espondilite AnquilosanteRESUMO
OBJECTIVES: Evidence on comorbidity prevalence in antiphospholipid syndrome (APS) and its difference from high comorbidity burden rheumatic diseases is limited. Herein, we compare multiple comorbidities between APS and RA. METHODS: A total of 326 patients from the Greek APS registry [237 women, mean age 48.7 (13.4) years, 161 primary APS (PAPS), 165 SLE-APS] were age/sex matched (1:2 ratio) with 652 patients from a Greek multicentre RA cohort of 3115 patients. Prevalence of cardiovascular (CV) risk factors, stroke, coronary artery disease (CAD), osteoporosis, diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), depression and neoplasms were compared between APS and RA patients using multivariate regression analysis. RESULTS: Ηyperlipidemia and obesity (ΒΜΙ ≥ 30 kg/m2) were comparable while hypertension, smoking, stroke and CAD were more prevalent in APS compared with RA patients. Osteoporosis and depression were more frequent in APS, while DM, COPD and neoplasms did not differ between the two groups. Comparison of APS subgroups to 1:2 matched RA patients revealed that smoking and stroke were more prevalent in both PAPS and SLE-APS vs RA. Hypertension, CAD and osteoporosis were more frequent only in SLE-APS vs RA, whereas DM was less prevalent in PAPS vs RA. Hyperlipidaemia was independently associated with CV events (combined stroke and CAD) in PAPS and SLE-APS, while CS duration was associated with osteoporosis in SLE-APS. CONCLUSION: Comorbidity burden in APS (PAPS and SLE-APS) is comparable or higher than that in RA, entailing a high level of diligence for CV risk prevention, awareness for depression and CS exposure minimization.
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Síndrome Antifosfolipídica/epidemiologia , Artrite Reumatoide/epidemiologia , Fatores de Risco de Doenças Cardíacas , Estudos de Casos e Controles , Comorbidade , Doença da Artéria Coronariana/epidemiologia , Depressão/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Grécia/epidemiologia , Humanos , Hiperlipidemias/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Obesidade/epidemiologia , Osteoporose/epidemiologia , Prevalência , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Análise de Regressão , Fatores de Risco , Fumar/epidemiologia , Acidente Vascular Cerebral/epidemiologiaRESUMO
The spondyloarthritides are a group of chronic systemic inflammatory joint diseases, the main types being ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Evidence accumulating during the last decades suggests that patients with AS or PsA carry an increased risk for cardiovascular disease and cardiovascular death. This risk appears to be mediated by systemic inflammation over and above classical cardiovascular risk factors. The excess cardiovascular risk in those patients has been formally acknowledged by scientific organizations, which have called physicians' attention to the matter. The application by Rheumatologists of new effective anti-rheumatic treatments and treat-to-target strategies seems to benefit patients from a cardiovascular point of view, as well. However, more data are needed in order to verify whether anti-rheumatic treatments do have an effect on cardiovascular risk and whether there are differences among them in this regard. Most importantly, a higher level of awareness of the cardiovascular risk is needed among patients and healthcare providers, better tools to recognize at-risk patients and, ultimately, commitment to address in parallel both the musculoskeletal and the cardiovascular aspect of the disease.
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Artrite Psoriásica/complicações , Doenças Cardiovasculares/etiologia , Sistema Cardiovascular/fisiopatologia , Inflamação/complicações , Espondilite Anquilosante/complicações , Animais , Anti-Inflamatórios/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/imunologia , Artrite Psoriásica/fisiopatologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/imunologia , Comorbidade , Fatores de Risco de Doenças Cardíacas , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/fisiopatologia , Estilo de Vida , Prognóstico , Medição de Risco , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/imunologia , Espondilite Anquilosante/fisiopatologiaRESUMO
We present a case of dermatomyositis together with polycythemia as initial manifestations of a particularly rare type of prostate cancer. A 69-year-old man was hospitalized for facial erythema and symptoms of fatigue. Physical evaluation, serum creatinine phosphokinase and electromyography were consistent with dermatomyositis. In parallel, the hemoglobin level was 18.5 g/dL, serum erythropoietin levels were low normal and no JAK2 mutation was found. Given a strong suspicion of a paraneoplastic syndrome the patient underwent abdominal computed tomography revealing a prostate mass, enlarged iliac lymph nodes and a fracture of L1 due to metastasis. The unusual paraneoplastic manifestations prompted a more thorough immunohistologic examination of the needle biopsy specimen taken from the prostate, which led to the diagnosis of large cell neuroendocrine prostate carcinoma. It is a most rare type of prostate cancer, carrying a poor prognosis. To our knowledge, this is the first case in the literature associating a neuroendocrine cancer of the prostate with dermatomyositis.
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BACKGROUND: The role of neutrophils in tumour biology is largely unresolved. Recently, independent studies indicated either neutrophil extracellular traps (NETs) or Tissue Factor (TF) involvement in cancer biology and associated thrombosis. However, their individual or combined role in colonic adenocarcinoma is still unexplored. METHODS: Colectomy tissue specimens and variable number of draining lymph nodes were obtained from ten patients with adenocarcinoma of the colon. NETs deposition and neutrophil presence as well as TF expression were examined by immunostaining. The effect of NETs on cancer cell growth was studied in in vitro co-cultures of Caco-2 cell line and acute myeloid leukemia primary cells. Proliferation and apoptosis/necrosis of cancer cells were analyzed by flow cytometry. RESULTS: TF-bearing NETs and neutrophil localization were prominent in tumour sections and the respective metastatic lymph nodes. Interestingly, neutrophil infiltration and NETs concentration were gradually reduced from the tumour mass to the distal margin. The in vitro-generated NETs impeded growth of cancer cell cultures by inducing apoptosis and/or inhibiting proliferation. CONCLUSIONS: These data support further the role of neutrophils and NETs in cancer biology. We also suggest their involvement on cancer cell growth.
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Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Infiltração de Neutrófilos/imunologia , Infiltração de Neutrófilos/fisiologia , Neutrófilos/imunologia , Neutrófilos/fisiologia , Células CACO-2 , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/fisiologia , Citometria de Fluxo , Humanos , Células Tumorais CultivadasRESUMO
OBJECTIVE: To investigate the total annual direct cost of patients with spondyloarthritis (SpA) in Greece. METHODS: Retrospective study with 156 patients diagnosed and followed up in the rheumatology clinic of the University Hospital of Ioannina. Sixty-four had ankylosing spondylitis (AS) and 92 had psoriatic arthritis (PsA). Health resource use for each patient was elicited through a retrospective chart review that documented the use of monitoring visits, medications, laboratory/diagnostic tests, and inpatient stays for the previous year from the date that the review took place. Costs were calculated from a third-party payer perspective and are reported in 2014 euros. RESULTS: The mean ± SD annual direct cost for the patients with SpA reached 8680 ± 6627. For the patients with PsA and AS, the cost was estimated to be 8097 ± 6802 and 9531 ± 6322, respectively. The major cost was medication, which represented 88.9%, 88.2%, and 89.3% of the mean total direct cost for SpA, AS, and PsA, respectively. The annual amount of the scheduled tests for all patients corresponded to 7.5%, and for those performed on an emergency basis, 1.1%. Further, the cost for scheduled and emergency hospitalization, as well as the cost of scheduled visits to an outpatient clinic, corresponded to 2.5% of the mean total annual direct cost for the patients with SpA. CONCLUSION: SpA carries substantial financial cost, especially in the era of new treatment options. Adequate access and treatment for patients with SpA remains a necessity, even in times of fiscal constraint. Thus, the recommendations of the international scientific organizations should be considered when administering high-cost drugs such as biological treatments.
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Anticorpos Monoclonais Humanizados/economia , Antirreumáticos/economia , Artrite Psoriásica/economia , Efeitos Psicossociais da Doença , Reembolso de Seguro de Saúde/economia , Espondiloartropatias/economia , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Antirreumáticos/uso terapêutico , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Estudos de Coortes , Análise Custo-Benefício , Feminino , Grécia , Custos Hospitalares , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Espondiloartropatias/diagnóstico , Espondiloartropatias/tratamento farmacológico , Centros de Atenção TerciáriaRESUMO
Golimumab, a fully human monoclonal antibody against tumour necrosis factor-α (TNF-α) is one of the newest biologics that has become available for the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Following the initial randomised double-blind placebo-controlled clinical trials, which demonstrated the efficacy and safety of the drug in the context of a limited patient sample and a relatively short time frame, golimumab has been the focus of continuous investigation through the extensions of the above-mentioned trials, new clinical trials and registries of biologic drug use in daily clinical practice. The review of this data and their inclusion in meta-analyses and indirect comparisons across TNF-α blockers suggest that golimumab possesses similar properties regarding efficacy and safety as the older monoclonal anti-TNF-α antibodies. The novelty of golimumab is perhaps its dosing regimen, i.e. subcutaneous self-administration once monthly, which allows for the least disturbance in the life of patients.
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Anticorpos Monoclonais/farmacologia , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Terapia Biológica , Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa , Antirreumáticos/farmacologia , Artrite Psoriásica/imunologia , Artrite Reumatoide/imunologia , Terapia Biológica/métodos , Terapia Biológica/tendências , Humanos , Avaliação de Resultados em Cuidados de Saúde , Espondilite Anquilosante/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologiaRESUMO
OBJECTIVES: The spondyloarthritides (SpA) are associated with an increased cardiovascular risk. We studied cardiovascular risk factors in patients with SpA. METHODS: The following risk factors were assessed in SpA patients and healthy controls: smoking, family history of premature ischemic heart disease, obesity, serum lipids, apolipoproteins, urate and carotid intima media thickness (IMT). RESULTS: Overall 150 patients (73 with ankylosing spondylitis [AS], 71 with psoriatic arthritis [PsA] and six with other SpA types) were included. Generally SpA patients were significantly more often smokers, while PsA patients had greater values of abdominal obesity. AS patients had significantly lower levels of triglyceride, HDL, ApoB, ApoE and Lp(a) and a higher atherogenic index (total cholesterol/HDL). PsA patients had significantly lower levels of HDL, ApoAI and ApoE, an elevated atherogenic index and higher serum urate. In multivariate analysis the atherogenic index was positively associated with SpA across all patient groups independently of smoking and other lipid parameters. Carotid IMT in SpA patients (0.71 mm) was higher than controls (0.63 mm, P=0.017), although after adjusting for smoking this ceased to be significant. Treatment of patients with previously untreated disease resulted in a small but significant decline in ApoB levels at 6 months (P=0.045), which, however, was no longer evident at 12 months. CONCLUSION: Spondyloarthritis patients are at a greater cardiovascular risk owing to the higher prevalence of smoking and a higher atherogenic index. PsA patients have more abdominal fat and higher urate levels. Immunosuppressive treatment of SpA produces minor and temporary effects on the lipid profile.
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Doenças Cardiovasculares/epidemiologia , Espondilartrite/epidemiologia , Adulto , Artrite Psoriásica/epidemiologia , Estudos Transversais , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Espondilartrite/tratamento farmacológico , Espondilite Anquilosante/epidemiologiaRESUMO
OBJECTIVES: The majority of patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are affected during their peak reproductive years. Tumor necrosis factor (TNF)α plays a pivotal role in the pathogenesis of both diseases. Today, anti-TNFα blockers are an essential treatment for these patients. To identify male patients who achieved pregnancy development during their management with anti-TNFα blockers (infliximab). METHODS: We reviewed the data of 65 patients with AS and 30 patients with PsA who were followed-up in our rheumatology outpatients clinic and they were on infliximab therapy between January 2001 and December 2010. RESULTS: We identified overall seven male patients with AS and three male patients with PsA who had fathered 14 healthy infants. Moreover, we recognized one man with PsA who was on infliximab and on concomitant therapy with MTX at the time of conception, whose wife had to proceed to therapeutic abortion due to congenital abnormalities of the fetus (hydrocephalia), while she was on the first trimester of pregnancy. CONCLUSIONS: We described male patients with AS and PsA who demonstrated no fertility problems while they were on infliximab treatment. The data designated in this report provide some supportive evidence for the safe use of infliximab in male patients who are affected of those inflammatory diseases during their peak reproductive years.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Infertilidade Masculina/induzido quimicamente , Espondiloartropatias/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/farmacologia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Humanos , Infliximab , Masculino , Espermatogênese/efeitos dos fármacosRESUMO
Adalimumab (ADA), a fully human monoclonal antibody against TNF-α is indicated for the treatment of rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, Crohn's disease, ulcerative colitis and psoriasis. In RA, it may be prescribed in combination with methotrexate or other disease-modifying antirheumatic drugs or as monotherapy. Studies comparing ADA with other TNF-α inhibitors are limited and are based mainly on meta-analyses of randomised controlled trials and large observational cohorts. In this study, the effectiveness and safety of ADA is compared with that of etanercept and infliximab.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Adalimumab , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Etanercepte , Humanos , Imunoglobulina G/uso terapêutico , Infliximab , Receptores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
OBJECTIVE: To investigate the efficacy, toxicity, and drug discontinuation in patients with psoriatic arthritis treated with anti-tumor necrosis factor agents. METHODS: Sixty-five patients with active disease were included in this open-label study. They had tender or swollen joint count ≥5, Psoriatic Arthritis Severity Index (PASI) score ≥10, and erythrocyte sedimentation rate ≥28 mm Hg/1st hour and/or C-reactive protein ≥10 mg/L. All were refractory to at least 2 disease-modifying antirheumatic drugs. Thirty were treated with infliximab, 25 with etanercept, and 10 with adalimumab. Infliximab (5 mg/kg body weight) was given intravenously at weeks 0, 2, 6, and every 8 weeks thereafter; etanercept was given subcutaneously (25 mg twice a week), while adalimumab was given subcutaneously (40 mg every other week) for a period of 5 years. Data concerning anti-tumor necrosis factor efficacy tolerability, adverse events, and drug discontinuation were recorded. The percentage of patients who achieved the Psoriatic Arthritis Response Criteria (PSARC), the improvement of PASI, the improvement according to the American College of Rheumatology (ACR) criteria, and the disease activity for 28 joint indices score (DAS-28) were recorded. RESULTS: After 5 years, PSARC was 60%, PASI 70 was 66.7%, PASI 90 was 63.3%, while ACR 50 was 56.7% for the patients treated with infliximab. Moreover, PsARC was 64%, PASI 70 and PASI 90 were 68%, while ACR 50 was 56% for those treated with etanercept. Furthermore, in the adalimumab group PsARC was 56%, PASI 70 and PASI 90 were 58% and 50%, respectively, while ACR 50 was 50%. Additionally, DAS-28 scores were significantly improved. Thirteen patients treated with infliximab, 6 with etanercept, and 5 patients with adalimumab were withdrawn. At the end of treatment, the survival of infliximab was 56.7%, for etanercept 76%, and for adalimumab 50%. CONCLUSION: All drugs were effective, safe, and well-tolerated. The clinical improvement was maintained through the 5 years with satisfying infliximab and adalimumab survival and high etanercept survival.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Imunoglobulina G/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Adulto , Anticorpos Monoclonais Humanizados , Artrite Psoriásica/sangue , Artrite Psoriásica/mortalidade , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Estudos de Coortes , Etanercepte , Feminino , Humanos , Infliximab , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
This report seeks to describe the clinical efficacy and safety of infliximab in a patient with psoriatic arthritis on hemodialysis and to review the literature on the topic. We present a patient with psoriatic arthritis on hemodialysis treated with infliximab and we review the literature. Our case includes a patient with severe psoriasis and dactylitis with chronic renal failure requiring regular hemodialysis. At presentation the patient had a psoriasis area and severity index (PASI) score of 35.1 and dactylitis affecting the right thumb. Evaluation of laboratory parameters revealed a slight increase of erythrocyte sedimentation rate (21 mm/h) and a mild normocytic anemia (Hct 36.4). The rest of the laboratory and imaging tests were within normal limits. Infliximab was initiated at the loading dose of 5 mg/kg body weight at weeks 0, 2, 6, and every 8 weeks thereafter. On retreatment at week 14 the PASI score was measured to 3.4. After the conclusion of 6 months of treatment, the reduction of PASI score was sustained reaching the point of 0.8. In addition, dactylitis, as well as laboratory parameters, showed a striking improvement. On the other hand, during the same period of time, no changes of renal functions were noted and no complications were reported and the patient continued his hemodialysis on a regular basis. Our case is in accordance with other reports supporting that infliximab treatment in patients undergoing hemodialysis can be safe, well tolerated, and effective. However, larger trials are needed to prove its use in these patients.