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BACKGROUND: In 2017, belimumab (BEL) was approved in subcutaneous (SQ) administration. The effectiveness after switching from intravenous (IV) to SQ and patient satisfaction in daily clinical practice has not been studied. During the pandemic, patient follow-up and treatment were significantly affected, and some patients need a change from IV to SQ. Our aim was to evaluate daily clinical practice satisfaction to SQ BEL therapy in patients previously treated IV BEL. We hypothesized that SQ BEL in SLE patients previously treated with IV BEL was similar in effectiveness and conferred higher satisfaction. METHODS: Observational, multicenter study, conducted in 7 reference centers in Catalonia. We included stable SLE patients (EULAR/ACR 2019) on treatment with SQ BEL and previous use of IV BEL (at least 3 months on IV BEL before switching). Since there are no well-validated tools for SQ BEL treatment satisfaction, we used RASQ-SQ, validated in patients with lymphoma who switched from IV Rituximab to SQ treatment, and modified for BEL treatment. RESULTS: Twenty-seven patients were included. The more prevalent clinical manifestations observed were related to the skin and joints and the patients had a mean baseline SLEDAI of 2.96 (SD 2.4) and SLICC score of 0.67 (SD 0.88). The median time from treatment with IV BEL before switching to SQ was 21 months (range). 84% of patients reported confidence in SQ BEL. 85.2% felt that treatment with SQ BEL was convenient or very convenient. 85% felt they had gained time with the change. 89% would recommend the SQ injection to other patients. Disease activity (mean SLEDAI) and remission rates remain stable after switching. No major new adverse effects were reported. CONCLUSIONS: Overall satisfaction, satisfaction with via of administration, and satisfaction with the time taken to receive BEL were higher for SQ BEL treatment. A switching SQ strategy is a reasonable alternative for BEL patients.
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Anticorpos Monoclonais Humanizados , Imunossupressores , Lúpus Eritematoso Sistêmico , Humanos , Imunossupressores/uso terapêutico , Resultado do Tratamento , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Satisfação PessoalRESUMO
Objetivo: Comparar el cambio en la actividad asistencial realizada en una consulta de enfermería reumatológica antes y durante la pandemia. Material y métodos: Estudio descriptivo y observacional de 254 pacientes consecutivos antes y 251 durante. Resultados: El tipo de visita programada presencial disminuyó durante la COVID-19 (46,5% vs. 1,6%), aumentando la visita programada telefónica (2,8% vs. 52,2%) y las consultas espontáneas a través del teléfono o email (28,3% vs. 45%). Las funciones realizadas en las programadas fueron el control del paciente estable (20% vs. 37%) y la gestión (12% vs. 38%). El motivo de consulta espontánea incrementó durante la COVID-19, sobre todo: dudas respecto a medidas de prevención y optimización de tratamiento (13,8% vs. 31,1%). Conclusiones: La primera ola de la COVID-19 generó en la consulta de enfermería un incremento global de todas las actividades: en el número de visitas/día, en el número de controles de pacientes estables, en gestión y en la resolución de dudas.(AU)
Objective: The COVID-19 pandemic has brought major changes to the model of patient care in Rheumatology. Our aim was to compare the change in the care delivered in a rheumatology nursing consultation before and during the pandemic. Material and methods: Descriptive and observational study in 254 patients before and in 251 during the pandemic outbreak. Results: The type of scheduled face-to-face visit decreased during COVID-19 (46.5% vs. 1.6%), with the number of scheduled telephone visits increasing (2.8% vs. 52.2%) and spontaneous consultations over the phone or email (28.3% vs. 45%). The functions performed in the programmed ones were the stable patient control (20% vs. 37%) and management (12% vs. 38%). The reason for spontaneous consultation increased during COVID-19, especially doubts regarding prevention measures and treatment optimization (13.8% vs. 31.1%). Conclusions: The first wave of COVID-19 brought to rheumatology nursing consultation a global increase in all activities in the number of visits per day, in the number of stable patient controls, in monitoring and answering patient concerns.(AU)
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Humanos , Pandemias , Betacoronavirus , Reumatologia , Consulta Remota , Enfermagem Ambulatorial , Visita a Consultório Médico , Quarentena , Atenção à SaúdeRESUMO
OBJECTIVE: The COVID-19 pandemic has brought major changes to the model of patient care in Rheumatology. Our aim was to compare the change in the care delivered in a rheumatology nursing consultation before and during the pandemic. MATERIAL AND METHODS: Descriptive and observational study. Patient care was registered before and during the COVID-19 outbreak. The variables collected were age, sex, prevalent rheumatic disease, type of visit and reason for consultation. RESULTS: 254 consecutive patients were included before the COVID-19 pandemic for 20 days and 251 patients during COVID-19 for 10 working days. The mean age was 61 years before and 57 during the pandemic. Of both groups, 74% were women. The most frequently attended pathologies before and during COVID-19 were rheumatoid arthritis and spondyloarthropathies. Scheduled face-to-face visits decreased during COVID-19 (46.5% versus 1.6%), with an increased number of phone scheduled visits (2.8% versus 52.2%) and spontaneous consultations either by phone or e-mail (28.3% versus 45%). The type of scheduled visits during COVID-19 were for stable diseases (20% versus 37%) and monitoring (12% versus 38%). The reason for spontaneous consultation increased during COVID-19 and were mainly doubts regarding prevention measures and treatment optimization (13.8% versus 31.1%). CONCLUSIONS: The first wave of COVID-19 brought to rheumatology nursing consultation a global increase in all activities in the number of visits per day, in the number of stable patient controls, in monitoring and answering patient concerns.
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COVID-19 , Doenças Reumáticas , Reumatologia , COVID-19/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Encaminhamento e Consulta , Doenças Reumáticas/epidemiologiaRESUMO
BACKGROUND: Different classification criteria for systemic lupus erythematosus (SLE) have been launched over the years. Our aim was to evaluate the performance of the EULAR/ACR-2019, SLICC-2012 and ACR-1997 classification criteria in a cohort of SLE patients with longstanding disease. METHODS: Descriptive observational study in 79 patients with established and longstanding SLE. The three classification criteria sets were applied to those patients. RESULTS: Of the 79 patients, 70 were women (88.6%), with a mean age of 51.8 ± 14 years and a mean disease duration of 15.2 ± 11.5 years. The sensitivity of the different criteria were: 51.9%, 87.3% and 86.1% for ACR-1997, SLICC-2012 and EULAR/ACR-2019, respectively. In total, 68 out of 79 patients (53.7%) met all three classification criteria; 11.4% did not meet any classification criteria and were characterized by low SLEDAI (0.6 ± 0.9), low SLICC/ACR Damage Index (0.88 ± 0.56) and fulfilling only skin domains, antiphospholipid antibodies or hypocomplementemia. To fulfill EULAR/ACR-2019 criteria was associated with low complement levels (p < 0.04), high anti-dsDNA levels (p < 0.001), presence of lupus nephritis III-IV (p < 0.05) and arthritis (p < 0.001). CONCLUSION: The EULAR/ACR-2019 classification criteria showed high sensitivity, similar to SLICC-2012, in SLE patients with longstanding disease. Patients with serological, articular or renal involvement are more likely to fulfill SLICC-2012 or EULAR/ACR-2019 criteria.
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Platelets (PLTs) can modulate the immune system through the release of soluble mediators or through interaction with immune cells. Monocytes are the main immune cells that bind with PLTs, and this interaction is increased in several inflammatory and autoimmune conditions, including systemic lupus erythematosus (SLE). Our aim was to characterize the phenotypic and functional consequences of PLT binding to monocytes in healthy donors (HD) and in SLE and to relate it to the pathogenesis of SLE. We analyzed the phenotypic and functional features of monocytes with non-activated and activated bound PLTs by flow cytometry. We observed that monocytes with bound PLTs and especially those with activated PLTs have an up-regulated HLA-DR, CD86, CD54, CD16 and CD64 expression. Monocytes with bound PLTs also have an increased capacity for phagocytosis, though not for efferocytosis. In addition, monocytes with bound PLTs have increased IL-10, but not TNF-α, secretion. The altered phenotypic and functional features are comparable in SLE and HD monocytes and in bound PLTs. However, the percentages of monocytes with bound PLTs are significantly higher in SLE patients and are associated with undetectable levels of anti-dsDNA antibodies and hematuria, and with normal C3 and albumin/creatinine levels. Our results suggest that PLTs have a modulatory influence on monocytes and that this effect may be highlighted by an increased binding of PLTs to monocytes in autoimmune conditions.
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Plaquetas/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Monócitos/metabolismo , Adulto , Idoso , Anticorpos Antinucleares/sangue , Antígenos CD/biossíntese , Apoptose , Feminino , Citometria de Fluxo , Antígenos HLA-DR/biossíntese , Humanos , Interleucina-10/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Masculino , Glicoproteínas de Membrana/biossíntese , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Neutrófilos/patologia , Fagocitose , Fenótipo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: The COVID-19 pandemic has brought major changes to the model of patient care in Rheumatology. Our aim was to compare the change in the care delivered in a rheumatology nursing consultation before and during the pandemic. MATERIAL AND METHODS: Descriptive and observational study in 254 patients before and in 251 during the pandemic outbreak. RESULTS: The type of scheduled face-to-face visit decreased during COVID-19 (46.5% vs. 1.6%), with the number of scheduled telephone visits increasing (2.8% vs. 52.2%) and spontaneous consultations over the phone or email (28.3% vs. 45%). The functions performed in the programmed ones were the stable patient control (20% vs. 37%) and management (12% vs. 38%). The reason for spontaneous consultation increased during COVID-19, especially doubts regarding prevention measures and treatment optimization (13.8% vs. 31.1%). CONCLUSIONS: The first wave of COVID-19 brought to rheumatology nursing consultation a global increase in all activities in the number of visits per day, in the number of stable patient controls, in monitoring and answering patient concerns.
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BACKGROUND: The concomitant presence of two autoimmune diseases - systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) - in the same patient is known as rhupus. We evaluated a group of patients with rhupus to clarify further their clinical, serological and immunogenic features in a multi-centre cohort. In addition, the study aimed to explore the utility of the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria in our group of patients with rhupus. METHODS: This was a cross-sectional study. We included rhupus patients from 11 different rheumatology departments, and compared them to SLE and RA patients at a ratio of 2:1. All information was recorded following a pre-established protocol. RESULTS: A total of 200 patients were included: 40 rhupus patients and 80 each of SLE and RA patients as controls. Disease duration was similar among SLE and rhupus groups (around 13 years), but the RA group had a significantly lower disease duration. Main clinical manifestations were articular (94.2%), cutaneous (77.5%) and haematological (72.5%). Rhupus patients had articular manifestations similar to those expected in RA. Only 10% of rhupus patients had renal involvement compared with 25% of those with SLE (p < 0.05), while interstitial lung disease was more common in patients affected by RA. The 2019 EULAR/ACR SLE criteria were met in 92.5% of the rhupus patients and in 96.3% of the SLE cohort (p > 0.05). Excluding the joint domain, there were no differences between the numbers of patients who met the classification criteria. CONCLUSION: Rhupus patients follow a particular clinical course, with full expression of both SLE and RA in terms of organ involvement, except for a lower prevalence of kidney affection. The new 2019 EULAR/ACR SLE criteria are not useful for differentiating SLE and rhupus patients. A new way of classifying autoimmune diseases is needed to identify overlapping clusters.
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Artrite Reumatoide/fisiopatologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Adulto , Idoso , Artrite Reumatoide/classificação , Artrite Reumatoide/imunologia , Estudos de Casos e Controles , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the polyclonal activation of B lymphocytes and the production of autoantibodies that cause immune complex-related inflammation. Immunological factors derived from platelets modulate B cell function in SLE disease. However, platelets do not only modify the immune system by soluble factors. The binding of platelets to lymphocytes can modulate immune response. Thus, we speculate that the binding of platelets to lymphocytes in SLE patients may play a role in abnormal B lymphocyte response and the pathogenesis of SLE. We observed that levels of lymphocytes with bound platelets were higher in SLE patients than in healthy donors (HD). In SLE patients, the percentage of B lymphocytes with bound platelets positively correlated with plasmatic levels of IgG, IgA, IL-10, and soluble CD40L and negatively correlated with IgM levels, though not in HD. Preswitched memory B lymphocytes were the subpopulation with more bound platelets. Lymphocytes with bound platelets from both HD and SLE patients had major levels of CD86 and BAFFR and a greater production of IL-10 than lymphocytes without bound platelets. However, only B lymphocytes with bound platelets from SLE patients had increased levels of IgG and IgA on their surface. SLE patients with a suggestive renal manifestation had the highest levels of B and T lymphocytes with bound platelets. These results suggest that the binding of platelets to lymphocytes plays a role in SLE disease and that controlling this binding may be a promising therapeutic approach.
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Linfócitos B/metabolismo , Linfócitos B/patologia , Plaquetas/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/patologia , Linfócitos/metabolismo , Linfócitos/patologia , Adulto , Ligante de CD40/sangue , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Interleucina-10/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
Soluble factors released from platelets can modulate the immune response of leukocytes. We and others have recently found that T lymphocytes with bound platelets have reduced proliferation and IFN-γ and IL-17 production. Thus, we speculate that if we induce the binding of platelets to lymphocytes, we will be able to regulate the inflammatory response. When we cocultured platelets with lymphocytes at different ratios, we were able to increase the percentage of lymphocytes with bound platelets. The coculture of platelets with lymphocytes in the presence of stimulation decreased the production of IFN-γ and TNF-α, T cell proliferation, and the expression of CD25, PD-L1, and SLAM. However, this coculture increased CD39 expression. All of these effects were dependent on the dose of platelets and operated indistinctly with platelets from different healthy donors. When platelets were cocultured in the same compartment with lymphocytes, we observed less IFN-γ and TNF-α production and T lymphocyte proliferation than in cultures with platelets separated from lymphocytes by a 0.4-µm pore size filter. The binding of platelets to lymphocytes was blocked with anti-P-selectin Abs, and when this occurred we observed higher IFN-γ and TNF-α production than in nonblocked conditions. The cocultures of platelets with synovial fluid cells from rheumatoid arthritis patients reduced inflammatory cytokine production and increased IL-10 production. These results suggest that platelet binding to lymphocytes effectively regulates T lymphocyte function. This mechanism could be easily applied to reduce inflammatory responses.
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Artrite Reumatoide/imunologia , Plaquetas/imunologia , Citocinas/biossíntese , Ativação Linfocitária/imunologia , Linfócitos T/imunologia , Técnicas de Cocultura , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To identify predictors of early response to tocilizumab (TCZ) in patients with active rheumatoid arthritis (RA) seen in daily routine clinical practice. METHODS: A multicenter ambispective observational study of 126 RA patients treated with TCZ as a first- or second-line biological therapy. The variables associated to achieve the therapeutic goal (remission defined as a DAS28-ESR < 2.6) at 3 and 6 months were identified using regression analysis. RESULTS: TCZ was administered as the first biologic in 26% of patients. Overall, 34% of patients received TCZ as monotherapy. EULAR response and remission were obtained in 82% and 31% of patients at 3 months and in 86% and 40% at 6 months. In the multivariate analysis, the predictive factors increasing the likelihood of clinical remission at 3 months were baseline ESR > 30 mm/h (OR = 19.07, 95% CI: 2.720-133.716), baseline CRP > 10 mg/L (OR = 4.95; 95% CI: 1.464-13.826), and the presence of extra-articular manifestations of the disease (OR = 15.45, 95% CI: 2.334-102.319). The factors that decreased it were higher concentrations of hemoglobin (OR = 0.53, 95% CI: 0.319-0.910), higher baseline DAS28-ESR (OR = 0.30, 95% CI: 0.145-0.635) and the number of previous DMARDs (OR = 0.41, 95% CI: 0.221-0.779), and biological therapies used (OR = 0.33, 95% CI: 0.155-0.734). The only factor that remained statistically significant at 6 months was higher baseline DAS28-ESR (OR = 0.55, 95% CI: 0.347-0.877). No relationship was found with the neutrophil count or with the RF or ACPA positivity. CONCLUSION: In routine clinical practice, strong acute phase response, the presence of extra-articular manifestations, and the number of previous DMARDs and biological therapies used may help to identify patients who will have a rapid response to TCZ. However, it is likely that no parameter will predict response if taken separately.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Resultado do TratamentoRESUMO
OBJECTIVE: In agreement with EULAR recommendations, a DMARD in combination with a biotherapy is the reference treatment because of the superior long-term clinical and radiographic outcomes. Methotrexate (MTX) is the cornerstone of combination therapy but is in some cases contra-indicated or poorly tolerated. This observational study aimed to compare the effectiveness and safety of TCZ in combination with either MTX or leflunomide (LEF) in the treatment of patients with active rheumatoid arthritis (RA) and an inadequate response to one or more DMARDs and/or biological agents in a real-world setting. METHODS: We performed an ambispective review of 91 patients with active RA who were routinely treated with TCZ plus MTX or LEF. A comparative study between the two combinations of treatment was performed at 6 months of follow-up considering 3 outcomes: improvement of RA disease activity, evolution of functional disability, and tolerability and side effect profile. RESULTS: Of the 91 patients, 62 received TCZ with MTX and 29 received TCZ with LEF. Eighty-one patients were followed for 6 months, and the remaining 10 patients discontinued treatment due to serious adverse events. At baseline, there were no significant differences between the groups in terms of the main clinical and laboratory data or in the number of previous DMARDs and biological agents used. At 6 months, there were no significant differences between the combinations in terms of disease activity and functional disability. Serious adverse events occurred in 11% and 10% of the patients treated in combination with MTX and LEF, respectively. CONCLUSION: Our preliminary data support the argument that LEF is an effective and safe (equivalent) alternative to MTX for combination treatment with TCZ.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Isoxazóis/uso terapêutico , Metotrexato/uso terapêutico , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Humanos , Isoxazóis/efeitos adversos , Leflunomida , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: Reproducible association of a functional polymorphism in FCGR2A with response to a TNF inhibitor (TNFi) in patients with rheumatoid arthritis (RA) led us to explore other FcγR functional polymorphisms. METHODS: Functional polymorphisms FCGR3A F158V, FCGR2B I223T and promoter VNTR in FCGRT were analyzed in up to 429 patients with RA. Response to TNFi was recorded during standard care at 3, 6 and 12 months of follow-up. Fixed effects meta-analysis of studies addressing FCGR3A F158V polymorphism, which is the most studied of these polymorphisms, was conducted with inverse variance weighting. RESULTS: None of the functional polymorphisms were associated with change in DAS28. Meta-analysis of the seven studies (899 patients) with available data addressing association of FCGR3A F158V with response to TNFi in RA showed no association (OR: 1.11, 95% CI: 0.8-1.5; p = 0.5). CONCLUSION: None of the three functional polymorphisms in FcγR genes showed association with response to TNFi in patients with RA. These negative results were obtained in spite of the larger size of this study relative to previous studies addressing the same polymorphisms. In addition, meta-analysis of FCGR3A F158V was also negative against the results provided by previous studies. Original submitted 17 September 2014; Revision submitted 9 December 2014.
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Artrite Reumatoide/genética , Antígenos de Histocompatibilidade Classe I/genética , Receptores Fc/genética , Receptores de IgG/genética , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
INTRODUCTION: We have hypothesized that incompatibility between the G1m genotype of the patient and the G1m1 and G1m17 allotypes carried by infliximab (INX) and adalimumab (ADM) could decrease the efficacy of these anti-tumor necrosis factor (anti-TNF) antibodies in the treatment of rheumatoid arthritis (RA). METHODS: The G1m genotypes were analyzed in three collections of patients with RA totaling 1037 subjects. The first, used for discovery, comprised 215 Spanish patients. The second and third were successively used for replication. They included 429 British and Greek patients and 393 Spanish and British patients, respectively. Two outcomes were considered: change in the Disease Activity Score in 28 joint (ΔDAS28) and the European League Against Rheumatism (EULAR) response criteria. RESULTS: An association between less response to INX and incompatibility of the G1m1,17 allotype was found in the discovery collection at 6 months of treatment (P = 0.03). This association was confirmed in the replications (P = 0.02 and 0.08, respectively) leading to a global association (P = 0.001) that involved a mean difference in ΔDAS28 of 0.4 units between compatible and incompatible patients (2.3 ± 1.5 in compatible patients vs. 1.9 ± 1.5 in incompatible patients) and an increase in responders and decrease in non-responders according to the EULAR criteria (P = 0.03). A similar association was suggested for patients treated with ADM in the discovery collection, but it was not supported by replication. CONCLUSIONS: Our results suggest that G1m1,17 allotypes are associated with response to INX and could aid improved therapeutic targeting in RA.
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Adalimumab/genética , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Imunoglobulina G/genética , Infliximab/genética , Adalimumab/uso terapêutico , Adulto , Antirreumáticos/uso terapêutico , Artrite Reumatoide/imunologia , Sequência de Bases , Feminino , Genótipo , Humanos , Alótipos de Imunoglobulina , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
OBJECTIVES: We aimed to assess a functional polymorphism in FCGR2A H131R, for association with the treatment response to Fc-containing inhibitors of tumor necrosis factor (TNF). METHODS: A total of 429 biologic-naive patients with rheumatoid arthritis collected in two sets (299 and 130) were treated during standard care with infliximab (INX), etanercept, or adalimumab. Response to the treatment was evaluated at 3, 6, and 12 months of follow-up as the change in the Disease Activity Score (DAS) 28 from baseline and as the response by the European League Against Rheumatism (EULAR) criteria. These variables were analyzed for association with linear and logistic regression models that included sex, inhibitors of TNF, and baseline DAS28 as covariates. RESULTS: Significant association was found between the FCGR2A H131R polymorphism and the response to treatment with INX, but not with the other two TNF inhibitors. The 131R allele was associated with a lower change in DAS28 (P=0.04-0.008 at different times) in the first set of patients and confirmed in the second group of patients (P=0.026 at 3 months of follow-up). Association was also found in the comparison between nonresponders and responders to INX by the EULAR criteria. CONCLUSION: We found an association of the FCGR2A 131R allele with poor response to INX. This finding could be of utility to understand the mechanisms behind treatment failure and contribute to biomarker panels for INX response prediction.
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Anticorpos Monoclonais/efeitos adversos , Artrite Reumatoide/genética , Estudos de Associação Genética , Receptores de IgG/genética , Adalimumab , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Feminino , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
INTRODUCTION: In this study, our aim was to elucidate the role of four polymorphisms identified in a prior large genome-wide association study (GWAS) in which the investigators analyzed the responses of patients with rheumatoid arthritis (RA) to treatment with tumor necrosis factor inhibitors (TNFi). The authors of that study reported that the four genetic variants were significantly associated. However, none of the associations reached GWAS significance, and two subsequent studies failed to replicate these associations. METHODS: The four polymorphisms (rs12081765, rs1532269, rs17301249 and rs7305646) were genotyped in a total of 634 TNFi-treated RA patients of Spanish Caucasian origin. Four outcomes were evaluated: changes in the Disease Activity Score in 28 joints (DAS28) after 6 and 12 months of treatment and classification according to the European League Against Rheumatism (EULAR) response criteria at the same time points. Association with DAS28 changes was assessed by linear regression using an additive genetic model. Contingency tables of genotype and allele frequencies between EULAR responder and nonresponder patients were compared. In addition, we combined our data with those of previously reported studies in a meta-analysis including 2,998 RA patients. RESULTS: None of the four genetic variants showed an association with response to TNFi in any of the four outcomes analyzed in our Spanish patients. In addition, only rs1532269 yielded a suggestive association (P = 0.0033) with the response to TNFi when available data from previous studies were combined in the meta-analysis. CONCLUSION: Our data suggest that the rs12081765, rs1532269, rs17301249 and rs7305646 genetic variants do not have a role as genetic predictors of TNFi treatment outcomes.