RESUMO
OBJECTIVES: The aim of this study was to investigate the relationship between serum infliximab (IFX) levels and changes of RF and ACPA levels in patients with rheumatoid arthritis (RA). METHODS: Enzyme-linked immunosorbent assays (ELISA) [Promonitor® IFX R1 (version 2) (Progenika Biopharma, Spain)] were used to measure drug levels and antidrug-antibodies (ADAb) in IFX RA-treated patients (n=19). Disease activity was assessed using DAS28. IgM rheumatoid factor (RF) and IgM, IgA and IgG anti-cyclic citrullinated peptide (ACPA) were determined through ELISA. RESULTS: A significant decrease in RF (p=0.01), ACPA IgG (p=0.007), IgM (p=0.01) and IgA (p=0.03) was observed in patients presenting adequate levels of serum IFX. No significant changes to RF or ACPA were observed in patients with undetectable IFX. CONCLUSIONS: Data from this study support the hypothesis that the anti-TNF antagonist IFX downregulates autoantibody levels in RA patients when IFX levels are detectable. Larger-scale studies need to be performed to establish RF and ACPA presence as therapeutic response predictive factors.
Assuntos
Anticorpos Antiproteína Citrulinada/sangue , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Infliximab/uso terapêutico , Peptídeos Cíclicos/imunologia , Fator Reumatoide/sangue , Adulto , Idoso , Antirreumáticos/sangue , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Biomarcadores/sangue , Regulação para Baixo , Monitoramento de Medicamentos/métodos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Infliximab/sangue , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Tempo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologia , Adulto JovemRESUMO
To identify features associated with long-term persistent remission in rheumatoid arthritis (RA) patients on tapered biological disease-modifying antirheumatic drugs (bDMARD) (tap-bDMARD) therapy. We carried out a 40-month (m) extension follow-up study of 77 RA patients from a previous 12 m tap-bDMARD study. Disease activity was assessed at baseline and every 3 months. Doppler US investigation of 42 joints for the presence and grade (0-3) of B-mode synovial hypertrophy (SH) and synovial power Doppler signal (i.e., Doppler synovitis) was performed before starting the tap-bDMARD strategy by a rheumatologist blinded to clinical and laboratory data. At the 40 m mark, 44 (57.1%) patients failed the tap-bDMARD strategy, while 33 (42.9%) succeeded. Patients who presented a failed tap-bDMARD had significantly longer disease duration, a longer time from symptom onset to synthetic (s) DMARD start, longer duration of sDMARD treatment, a greater number of sDMARDs, and a higher baseline DAS28 and SDAI than patients with successful tap-bDMARD at 40 months. In logistic regression analysis, the presence of baseline Doppler synovitis, a DAS28 ≥ 2.2, and the presence of rheumatoid factor were identified as predictors of tap-bDMARD failure at 40 m. In those patients who succeed tap-bDMARD at 12 m, a smoking habit was significantly more frequently found in tap-bDMARD failures at 40 m. Our results showed that DAS28 and the presence of Doppler synovitis, RF and a smoking habit predicted long-term tap-bDMARD failure.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Sinovite/diagnóstico por imagem , Idoso , Antirreumáticos/farmacologia , Artrite Reumatoide/diagnóstico por imagem , Produtos Biológicos/farmacologia , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Indução de Remissão , Fator Reumatoide/sangue , Fator Reumatoide/efeitos dos fármacos , Fatores de Tempo , Falha de Tratamento , Ultrassonografia Doppler/métodosRESUMO
OBJECTIVES: To investigate the presence of biomechanical abnormalities and ultrasound (US)-detected inflammation and damage in low disease or remission status rheumatoid arthritis (RA) patients with foot complaints. METHODS: We recruited 136 subjects with foot complaints. Sixty-two were biologic disease-modifying antirheumatic drug-treated RA patients presenting Disease Activity Score-determined remission or low disease activity while the remaining 74 were gender matched controls without rheumatic or musculoskeletal disorders. Both groups underwent a comprehensive podiatric, biomechanical and B-mode and Doppler US assessment of the feet. RESULTS: Most RA patients and controls were female (77.4% and 83.8%, respectively). There was no statistical difference in the proportion of obese subjects in either group (p=0.792). Inappropriate shoes were used by 50.0% of RA patients and 33.8% of controls (p=0.080). Talalgia, particularly heel pain, was more frequent in the control group, with associated talalgia and metatarsalgia being more prevalent in the RA group (p<0.05). The RA patient group was also more likely to present greater foot deformity, more limited joint movement and biomechanical abnormalities than the controls (p<0.05). US inflammatory and structural changes were significantly more frequent in RA patients than in controls (p<0.05). US structural involvement was significantly associated with limited joint mobility and pathologic biomechanical tests only in RA patients (p<0.05). CONCLUSIONS: RA foot complaints seemed to be linked to US-detected RA involvement and biomechanical abnormalities. Podiatric and US assessments can be useful to help the clinician to optimise the management of RA patients in remission/low disease activity with foot complaints.
Assuntos
Artrite Reumatoide , Deformidades Adquiridas do Pé , Articulações do Pé/diagnóstico por imagem , Metatarsalgia/diagnóstico , Adulto , Idoso , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/fisiopatologia , Fenômenos Biomecânicos/fisiologia , Feminino , Deformidades Adquiridas do Pé/diagnóstico , Deformidades Adquiridas do Pé/etiologia , Deformidades Adquiridas do Pé/fisiopatologia , Articulações do Pé/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Ortopedia/métodos , Medição da Dor/métodos , Amplitude de Movimento Articular , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Ultrassonografia Doppler/métodosRESUMO
OBJECTIVES: To evaluate biomechanical and ultrasound (US) abnormalities in SLE patients as compared with controls and to assess the relationship between these abnormalities and SLE activity. METHODS: Fifty-four consecutive female patients with SLE with and without foot pain and 60 female controls (30 with foot pain and 30 without foot pain) were recruited. SLE activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). SLE patients and controls blindly underwent a comprehensive podiatric, biomechanical and US evaluation of the feet. US assessment included detection of B-mode synovitis, tenosynovitis, enthesopathy, bone changes and synovial, tenosynovial and entheseal power Doppler (PD) signal. RESULTS: Thirty-one (57.4%) SLE patients had bilateral foot pain and 5 (9.3%) had unilateral foot pain. Metatarsalgia was the most common location for pain but without significant difference between groups (p=0.284). Toe joint deformities were significantly more common in SLE feet as compared with control feet (p<0.0005). SLE feet showed significantly more biomechanical abnormalities than control feet (p<0.05). B-mode synovitis in the tibiotalar joint was strongly associated with having SLE (p<0.0005) and the presence of synovial PD signal in the MTP joints was found only in painful feet of SLE patients. SLEDAI was significantly higher in patients with foot pain than in those with painless feet (p=0.008). However, SLEDAI did not discriminate between patients with and without biomechanical or US abnormalities. CONCLUSIONS: SLE patients showed more biomechanical and US abnormalities in the feet than controls, which were not captured by standardised assessment of the disease activity.
Assuntos
Deformidades Adquiridas do Pé/etiologia , Pé , Lúpus Eritematoso Sistêmico/complicações , Dor/etiologia , Autoanticorpos/sangue , Biomarcadores/sangue , Fenômenos Biomecânicos , Estudos de Casos e Controles , Estudos Transversais , Feminino , Pé/diagnóstico por imagem , Pé/fisiopatologia , Deformidades Adquiridas do Pé/sangue , Deformidades Adquiridas do Pé/diagnóstico por imagem , Deformidades Adquiridas do Pé/fisiopatologia , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Dor/sangue , Dor/diagnóstico por imagem , Dor/fisiopatologia , Medição da Dor , Podiatria/métodos , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Ultrassonografia DopplerRESUMO
This cross-sectional observational study aimed to explore the relationship between B cell count and ultrasound (US)-detected synovitis, in patients with rheumatoid arthritis treated with rituximab. Thirty-seven consecutive RA patients treated with RTX were recruited for the study. The patients underwent clinical [i.e., Disease Activity Score 28 joints (DAS28)], laboratory, and US assessment of 12 joints. Each joint was semiquantitatively (0-3) scored on B-mode and power Doppler mode. The scores were summed, and a global index was created for BM (BMS) and PD scores (PDI) synovitis. BM subclinical synovitis was evident in all patients, with PD synovial signal detected in 16 patients (43.2 %). No correlation was found between DAS28 and US scores. B cells were detected in 27 (72.9 %) patients, but there was no association in the mean B cell count and disease activity as measured by DAS28 (DAS28 < 2.6 = 34.53, DAS28 > 2.6 = 49.45, p = 0.52) and PDI score (PDI < 1 = 49.48, PDI > 1 = 35.44, p = 0.54). There was no correlation between the B cell count and DAS28, BMS, and PDI (r = 0.020, p = 0.907; r = -0.151, p = 0.371; r = -0.099, p = 0.558, respectively). In RTX-treated RA patients, no relationship could be established between US-detected synovitis and peripheral blood B cell count.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Linfócitos B/efeitos dos fármacos , Articulações/efeitos dos fármacos , Rituximab/uso terapêutico , Sinovite/tratamento farmacológico , Ultrassonografia Doppler , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/imunologia , Linfócitos B/imunologia , Estudos Transversais , Avaliação da Deficiência , Feminino , Humanos , Articulações/diagnóstico por imagem , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Sinovite/sangue , Sinovite/diagnóstico por imagem , Sinovite/imunologia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To investigate the predictive value of synovitis detected by Doppler US in relation to failed tapering of biologic therapy (BT) in RA patients in sustained clinical remission. METHODS: A total of 77 RA patients (52 women, 25 men) in sustained clinical remission, treated with a stable dosage of BT were prospectively recruited. BT was tapered according to an agreed strategy implemented in clinical practice (i.e. increasing the interval between doses for s.c. BT and reducing the dose for i.v. BT). BT tapering failure was assessed at 6 and 12 months. Doppler US investigation of 42 joints for the presence and grade (0-3) of B-mode synovial hypertrophy and synovial power Doppler signal (i.e. Doppler synovitis) was performed at baseline by a rheumatologist blinded to clinical and laboratory data. Hand and foot radiographs were obtained at baseline and at 12-month follow-up. RESULTS: Of the 77 patients, 46 (59.7%) were on s.c. BT and 31 (40.3%) on i.v. BT. At 12 months, 35 patients (45.5%) presented BT tapering failure, 23 of them (29.9% of all patients) in the first 6 months of BT tapering. In logistic regression analysis, the baseline DAS28 and the global score of Doppler synovitis were identified as independent predictors of BT tapering failure at 12 and 6 months. The presence of Doppler synovitis was the strongest predictor for BT tapering failure. No patient showed radiographic progression. CONCLUSION: Our results suggest that the presence of Doppler-detected synovitis may predict BT tapering failure in RA patients in sustained clinical remission.
Assuntos
Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Membrana Sinovial/diagnóstico por imagem , Sinovite/diagnóstico por imagem , Ultrassonografia Doppler/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Articulações do Pé/diagnóstico por imagem , Articulação da Mão/diagnóstico por imagem , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Radiografia , Sinovite/diagnóstico , Fatores de Tempo , Falha de Tratamento , Resultado do TratamentoRESUMO
OBJECTIVES: Infliximab (IFX) and adalimumab (ADL) drug levels and anti-drug antibodies (ADA) are assessed using a variety of techniques, therefore, results cannot accurately be compared for clinical purposes. The aim of this study was to test two infliximab (IFX) and adalimumab (ADL) ELISA versions, for drug levels and ADA, to see whether they yield similar results. METHODS: ELISA versions [Promonitor® IFX R1 and R2 (V.1), Promonitor® IFX and Anti-IFX (V.2); Promonitor® ADL R1 and R2 (V.1), Promonitor® ADL and Anti-ADL (V.2) kits (Progenika Biopharma, Spain)] were used to measure drug levels and ADA in IFX (n=24) and ADL (n=24) rheumatoid arthritis-treated patients in three independent laboratories. Quantitative and qualitative agreements were evaluated using intraclass correlation coefficients (ICC), and Cohen's Kappa (κ) respectively. The Bland-Altman plots assessed differences between V.1 and V.2. RESULTS: Interlaboratory agreement (ICC/κ) with V.1 was poor for IFX (0.66/0.62) and ADL (0.69/0.52) drug levels; meanwhile, high agreement was found with V.2 for IFX (0.98/0.95) and ADL (0.094/1.00). Comparison between V.1 and V.2 in each laboratory resulted in systematically higher values in V.2 than in V.1 and poor agreement (ICC/κ ranges) for IFX (0.12-0.7/ 0.19-0.42) and ADL (0.69-0.89 /0.50-0.73). CONCLUSIONS: Qualitative measurements result in better agreement, as evidenced in our study. Greater agreement in V.2 compared with V.1 for IFX and ADL levels could be due to a better tune up. Further studies are required to standardise methods to establish therapeutic reference ranges.
Assuntos
Adalimumab/sangue , Antirreumáticos/sangue , Artrite Reumatoide/sangue , Monitoramento de Medicamentos/normas , Ensaio de Imunoadsorção Enzimática/normas , Infliximab/sangue , Ensaio de Proficiência Laboratorial/normas , Adalimumab/imunologia , Anticorpos/sangue , Antirreumáticos/imunologia , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Estudos Transversais , Humanos , Infliximab/imunologia , Variações Dependentes do Observador , Valor Preditivo dos Testes , Indicadores de Qualidade em Assistência à Saúde/normas , Reprodutibilidade dos Testes , Espanha , Resultado do TratamentoRESUMO
There are various immunosorbent assays which can be used to determine infliximab (IFX) levels. Results vary between assays complicating reliability in everyday clinical practice. The aim of this study was to determine whether quantitative or qualitative assay data prove more accurate in the assessment of infliximab levels in AS patients. We analyzed 40 serum samples, taken prior to infusion, from AS patients who had been undergoing IFX therapy as a first-line of biological treatment for more than a year. IFX levels and IFX-anti-drug antibodies (ADA) were measured using two different ELISA assays [Promonitor IFX R1 and R2 (version 1), Promonitor IFX and anti-IFX (version 2) (Progenika Biopharma, Spain)] strictly following the manufacturer's guidelines. Cohen's unweighted kappa and the intraclass correlation coefficient determined qualitative and quantitative agreement for serum levels in version 1 and version 2. Bland-Altman plots were drawn to compare both assays. The comparison of data measuring IFX levels for version 1 and version 2 resulted in questionable quantitative agreement (ICC 0.659; 95% CI 0.317-0.830) and moderate qualitative agreement (κ 0.607; 95% CI 0.387-0.879) owing to systematically higher values in version 2 than version 1. Version 2 consistently detected higher levels of infliximab, particularly when analyzed in a quantitative context. Further research is needed to synchronize cutoff levels between essays and diseases so therapeutic drug ranges can be established.
Assuntos
Monitoramento de Medicamentos/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Imunossupressores/sangue , Imunossupressores/uso terapêutico , Infliximab/sangue , Infliximab/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Espondilite Anquilosante/sangue , Espondilite Anquilosante/diagnósticoRESUMO
OBJECTIVE: The aim of this study was to investigate the influence of the pharmacokinetics of s.c. anti-TNF agents on the grade of US-detected synovitis in RA patients. METHODS: Fifty RA patients were prospectively recruited from the Biologic Therapy Unit of our hospital. Inclusion criteria were being in treatment with s.c. anti-TNF agents and having had neither changes in therapy nor local corticosteroid injections in the previous 3 months. Patients underwent clinical, laboratory [28-joint DAS (DAS28) and Simplified Disease Activity Index (SDAI)] and US assessment at two time points, i.e. at peak plasma drug concentration and at trough plasma drug concentration. US assessments were performed blindly to the anti-TNF agent, the administration time and the clinical and laboratory data. Twenty-eight joints were investigated for the presence and grade (0-3) of B-mode synovitis and synovial power Doppler signal. Global indices for B-mode synovitis (BSI) and Doppler synovitis (DSI) were calculated for 12 joints and for wrist-hand-ankle-foot joints. B-mode US remission was defined as a BSI <1 and Doppler US remission as a DSI <1. RESULTS: There were no significant differences between the clinical, laboratory and B-mode and Doppler US parameters at peak time and trough time (P = 0.132-0.986). There were no significant differences between the proportion of patients with active disease and those in remission according to DAS28, SDAI, B-mode US and Doppler US at peak time and trough time assessments (P = 0.070-1). CONCLUSION: Our results suggested that s.c. anti-TNF pharmacokinetics do not significantly influence US-scored synovitis in RA patients.
Assuntos
Antirreumáticos/farmacocinética , Artrite Reumatoide/tratamento farmacológico , Sinovite/diagnóstico por imagem , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/complicações , Artrite Reumatoide/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Sinovite/tratamento farmacológico , Sinovite/etiologia , Ultrassonografia Doppler , Adulto JovemRESUMO
OBJECTIVES: The aim of this paper is to assess the usefulness of measuring serum levels of adalimumab (ADL) and anti-ADL antibodies in 57 patients with rheumatoid arthritis (RA) treated with ADL for at least 3 months in daily practice. METHODS: All patients received concomitant disease-modifying anti-rheumatic drug (DMARD). Receiver-operator characteristics (ROC) analysis was used to obtain the cut-off value of ADL for low disease activity (DAS28-ESR ≤3.2). RESULTS: Anti-ADL antibodies were detected in 4 (7%) patients with a mean (SD) DAS28 score of 4.6 (0.9). Patients with positive anti-ADL antibodies had significantly lower levels of ADL and higher DAS28 scores than those with negative antibodies. Patients with DAS28 ≤3.2 as compared with patients with DAS28 >3.2 showed significantly better SDAI score, higher serum concentrations of ADL and none of them showed anti-ADL antibodies. The cut-off of serum level of ADL for DAS28 <3.2 was 4.3 mg/L. According to serum levels of ADL, patients were grouped into group 1 (low level) <5.5 mg/L, group 2 (medium level) 5.5-11.3 mg/L and group 3 (high level) >11.3 mg/L. Patients in the medium group were closed to clinical remission (median DAS28 2.7) and patients in the high group were on clinical remission (DAS28 2.1). CONCLUSIONS: Serum levels of ADL should be maintained >4.3 mg/L. In patients with ADL levels >11.3 mg/L, a decrease of the dose of ADL or an increase in the interval between doses may be planned. The presence of anti-ADL antibodies was associated with a loss of clinical efficacy of ADL.
Assuntos
Anticorpos Monoclonais Humanizados/sangue , Antirreumáticos/sangue , Artrite Reumatoide/tratamento farmacológico , Monitoramento de Medicamentos , Adalimumab , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/imunologia , Antirreumáticos/administração & dosagem , Antirreumáticos/imunologia , Área Sob a Curva , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Espanha , Fatores de Tempo , Resultado do TratamentoRESUMO
Due to their suppressive capacity, regulatory T cells (Tregs) have attracted growing interest as an adoptive cellular therapy for the prevention of allograft rejection, but limited Treg recovery and lower quality of adult-derived Tregs could represent an obstacle to success. To address this challenge, we developed a new approach that provides large quantities of Tregs with high purity and excellent features, sourced from thymic tissue routinely removed during pediatric cardiac surgeries (thyTregs). We report on a 2-year follow-up of the first patient treated worldwide with thyTregs, included in a phase I/II clinical trial evaluating the administration of autologous thyTreg in infants undergoing heart transplantation. In addition to observing no adverse effects that could be attributed to thyTreg administration, we report that the Treg frequency in the periphery was preserved during the 2-year follow-up period. These initial results are consistent with the trial objective, which is to confirm safety of the autologous thyTreg administration and its capacity to restore the Treg pool.
Assuntos
Transplante de Coração , Linfócitos T Reguladores , Adulto , Humanos , Lactente , Rejeição de Enxerto , Transplante HomólogoRESUMO
Several genome-wide association studies have identified a polymorphism located 35 kb upstream of the coding region of HLA-C gene (rs9264942; termed -35 C/T) as a host factor significantly associated with the control of HIV-1 viremia in untreated patients. The potential association of this host genetic polymorphism with the viral reservoirs has never been investigated, nor the association with the viral control in response to the treatment. In this study, we assess the influence of the polymorphism -35 C/T on the outcome of virus burden in 183 antiretroviral-naïve HIV-1-infected individuals who initiated antiviral treatment (study STIR-2102), analyzing HIV-1 RNA viremia and HIV-1 DNA reservoirs. The rs9264942 genotyping was investigated retrospectively, and plasma levels of HIV-1 RNA and peripheral blood mononuclear cell- (PBMC-) associated HIV-1 DNA were compared between carriers and noncarriers of the protective allele -35 C before antiretroviral therapy (ART), one month after ART and at the end of the study (36 months). HIV-1 RNA and HIV-1 DNA levels were both variables significantly different between carriers and noncarriers of the allele -35 C before ART. HIV-1 DNA levels remained also significantly different one month posttherapy. However, this protective effect of the -35 C allele was not maintained after long-term ART.
Assuntos
Reservatórios de Doenças/virologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , HIV-1/fisiologia , Antígenos HLA-C/genética , Adulto , Antivirais/uso terapêutico , Doenças Assintomáticas , Doença Crônica , DNA Viral/sangue , Feminino , Seguimentos , Genótipo , Interações Hospedeiro-Patógeno/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , RNA Viral/sangue , ViremiaRESUMO
Although advances in biological medicine have seen significant progress in the treatment of autoimmune and inflammatory disease, many patients do not experience a satisfactory response. Hence, there are two challenges facing the medical research community. The first is to continue development in the field of existing biological therapies, such as monoclonal antibodies. The second is to open new frontiers of research and explore treatment alternatives for non-responders to other therapies. Attention has increasingly turned to the therapeutic potential of small molecule weight kinase inhibitors (SMKIs), currently used extensively in oncology and haematology. Initial research into the therapeutic value of SMKIs for autoimmune and inflammatory diseases has been encouraging. SMKIs are taken orally, which reduces cost for the health provider, and could increase compliance for the patient. This is why research is now focusing increasingly on SMKIs as a new generation line of treatment in these diseases. Tofacitinib, an inhibitor of Janus-kinase, is currently the only drug approved for the treatment of rheumatoid arthritis by FDA. However, much more needs to be done to understand the intracellular signalling pathways and how these might affect disease progression before solid conclusions can be drawn.
Assuntos
Doenças Autoimunes/tratamento farmacológico , Inflamação/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Administração Oral , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Doenças Autoimunes/metabolismo , Humanos , Inflamação/metabolismo , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Transdução de Sinais , Resultado do TratamentoRESUMO
The primary objective of this study was to describe and compare clinical and musculoskeletal (MS) ultrasound (US) features between psoriatic arthritis (PsA) patients treated with full and tapered dosage of biologic (b) disease-modified antirheumatic drugs (DMARDs). The secondary objective was to compare clinical and MSUS features between PsA patients treated with bDMARDs with and without concomitant synthetic (s) DMARDs. We evaluated 102 patients with PsA treated with bDMARDs. The bDMARD dosage tapering had been made in patients with a maintained remission or minimal disease activity (MDA) according to their attending rheumatologist and with the patient acceptance. The bDMARD tapering consisted of the following: increase the interval between doses for subcutaneous bDMARDs or reduction of the dose for intravenous bDMARDs. The clinical evaluation consisted of a dermatologic and rheumatologic assessment of disease activity. The presence of B-mode and Doppler synovitis, tenosynovitis, enthesopathy, and paratenonitis was investigated by a rheumatologist blinded to drug dosage, clinical assessments, and laboratory results. Seventy-four (72.5 %) patients received full dosage of bDMARDs and 28 (27.5 %) received tapered dosage. The duration with biologic therapy and with current biologic therapy was significantly higher in patients with tapered dosages (p = 0.008 and p = 0.001, respectively). We found no significant differences between clinical, laboratory, and US variables, both for BM and CD between patients with full and tapered dosage and between patients with and without concomitant sDMARD. Clinical assessment, MSUS variables, and MDA status are similar in patients receiving full and tapered dosage of bDMARDs.
Assuntos
Antirreumáticos/administração & dosagem , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/administração & dosagem , Quimioterapia de Manutenção/métodos , Sinovite/tratamento farmacológico , Tenossinovite/tratamento farmacológico , Adalimumab/administração & dosagem , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Artrite Psoriásica/diagnóstico por imagem , Estudos Transversais , Articulação do Cotovelo/diagnóstico por imagem , Etanercepte/administração & dosagem , Feminino , Articulações do Pé/diagnóstico por imagem , Articulação da Mão/diagnóstico por imagem , Humanos , Infliximab/administração & dosagem , Articulação do Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Sinovite/diagnóstico por imagem , Tenossinovite/diagnóstico por imagem , Resultado do Tratamento , Ultrassonografia DopplerAssuntos
Síndrome Antifosfolipídica/diagnóstico , Inibidor de Coagulação do Lúpus/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Complicações na Gravidez/prevenção & controle , Trombose/prevenção & controle , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/complicações , Doenças Assintomáticas , Biomarcadores/sangue , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/etiologia , Medição de Risco , Fatores de Risco , Trombose/sangue , Trombose/etiologiaRESUMO
Rheumatoid arthritis (RA) is a chronic systemic disease that leads to increases in health system economic burden through direct and indirect costs, including chronic treatment, reduced productivity and premature mortality. Anti-TNF agents have represented a major advance in the treatment of RA. The most commonly used (adalimumab, etanercept and infliximab) have demonstrated their cost-effectiveness at label doses. However, physicians may need to adapt the treatment by increasing the dose when a drug is not effective enough or by reducing it when there is a sustained effectiveness. In a cross-sectional study conducted in our hospital in which information from RA patients treated with anti-TNF drugs under conventional and modified doses were collected, the authors analyzed the costs of the medication in order to estimate the mean patient-year cost, the annual costs related to clinical efficacy and the cost per responder patient to anti-TNF treatment when dosage modification is undertaken in daily clinical practice.