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1.
Arthritis Res Ther ; 22(1): 284, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33298140

RESUMO

BACKGROUND: Biological therapies have improved the clinical course and quality of life of rheumatoid arthritis (RA) patients. Despite the availability and effectiveness of these treatments, some patients experience multiple failures to biologic disease-modifying antirheumatic drugs (bDMARDs), constituting a particular challenge to clinicians. OBJECTIVES: This study aims to determine the percentage of rheumatoid arthritis (RA) patients who fail to respond to subsequent bDMARDs, describe their characteristics, and identify specific baseline and early features during the first bDMARD as possible predictors of consecutive multiple bDMARD failure. METHODS: This is a longitudinal study involving RA patients from the prospective biological cohort drawn from the La Paz University Hospital RA Registry (RA-Paz), starting a bDMARD during the years 2000 to 2019. Patients who presented insufficient response (due to primary or secondary inefficacy) to at least three bDMARDs or two bDMARDs with different mechanism of action were considered multi-refractory (MR-patients). Patients who achieved low disease activity or remission (by DAS-28) with the first bDMARD and maintained this over a follow-up period of at least 5 years were considered non-refractory (NR-patients). RESULTS: A total of 41 out of 402 (10%) patients were MR-patients and 71 (18%) NR-patients. In the multivariate analysis, the presence of erosions, younger age, higher baseline DAS-28 and mostly achieving delta-DAS < 1.2 after 6 months of the first bDMARD (OR 11.12; 95% CI 3.34-26.82) were independently associated with being MR-patients to bDMARDs. CONCLUSIONS: In our cohort, 10% of patients with RA were observed to have multi-refractoriness to bDMARDs. This study supports the contention that younger patients with erosive disease and especially the early absence of clinical response to the first bDMARDs are predictors of multi-refractoriness to consecutive biologics. Hence, patients with these characteristics should be monitored more closely and may benefit from personalized treatments.

3.
Arthritis Rheumatol ; 2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33381897

RESUMO

OBJECTIVES: We aimed to identify MHC susceptibility factors for the anti-carbamylated protein (anti-CarP) antibody-positive RA. Previously, only the HLA-DRB1 alleles have been assessed. METHODS: The analysis was restricted to the anti-CCP- patients because the anti-CCP status dominates it otherwise. The genotypes for about 8000 MHC biallelic variants were obtained by dense genotyping and imputation in 1821 anti-CCP- patients and 6821 population controls from Spain, Sweden, and the Netherlands. Their association with the anti-CarP status was tested with logistic regression and combined with inverse-variance meta-analysis. Significance was assessed according to the study-level threshold (p < 2.0 x10-5 ). RESULTS: The HLA-B*08 allele and its correlated amino-acid variant Asp-9 were significantly associated with the anti-CarP+ /anti-CCP- patients (p < 3.8 x10-7 ; I2 = 0). These associations were specific relative to three comparators, the population controls, the anti-CarP- /anti-CCP- patients, and the anti-CCP- patients positive for other anti-citrullinated protein antibodies (ACPA). Therefore, they could be separated from other antibody-defined RA subsets previously associated with the HLA-B*08 allele. No other MHC variant remained associated with the anti-CarP+ /anti-CCP- patients after accounting for the HLA-B*08 allele. Specifically, the reported HLA-DRB1*03 association was observed at a level comparable to previous reports, but it was attributable to linkage disequilibrium. CONCLUSION: Our results identify HLA-B*08 carrying Asp-9 as the most associated MHC locus with anti-CarP+ /anti-CCP- RA. This knowledge contributes to clarify the role of the HLA in susceptibility to RA subsets by shaping the spectrum of RA autoantibodies.

4.
Sci Rep ; 10(1): 19263, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-33159095

RESUMO

The presence of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) autoantibodies contributes to the current rheumatoid arthritis (RA) classification criteria. These criteria involve stratification on antibody levels, which limits reproducibility, and underperform in the RA patients without RF and anti-CCP. Here, we have explored if two anti-acetylated peptide antibodies (AAPA), anti-acetylated lysine (AcLys) and anti-acetylated ornithine (AcOrn), could improve the performance of the current criteria. The analysis was done in 1062 prospectively-followed early arthritis (EA) patients. The anti-AcOrn were more informative than the anti-AcLys, the conventional RA antibodies and the anti-carbamylated protein antibodies. The anti-AcOrn produced a classification that did not require antibody levels and showed improved specificity (77.6% vs. 72.6%, p = 0.003) and accuracy (79.0% vs. 75.8%, p = 0.002) over the current criteria. These improvements were obtained with a scoring system that values concordance between anti-AcOrn, RF and anti-CCP. No significant gain was obtained in sensitivity (80.2% vs. 78.8%, p = 0.25) or in improving the classification of the RA patients lacking RF and anti-CCP, although the anti-AcOrn ranked first among the analysed new antibodies. Therefore, the anti-AcOrn antibodies could contribute to the improvement of RA classification criteria by exploiting antibody concordance.

5.
Ther Adv Musculoskelet Dis ; 12: 1759720X20971889, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240404

RESUMO

Aims: First, to compare clinical features and biological disease modifying anti-rheumatic drugs (bDMARDs) response in patients with axial spondyloarthritis (axSpA) and axial psoriatic arthritis (axPsA). Second, to identify possible predictors of treatment response in both entities. Methods: One-year follow-up, observational, single-center study including all patients with axSpA or axPsA who started bDMARDs therapy. Clinical features were collected at baseline while disease activity was measured at baseline, 6 and 12 months by the Ankylosing Spondylitis Disease Activity Score and the Physician Global Assessment. The frequency of patients achieving inactive disease (ID), low disease activity (LDA), high or very high disease activity and clinical improvement were compared between axSpA and axPsA. Baseline predictor factors for achieving treatment response were identified through regression models, using odds ratio (OR) as an estimate. Results: In total, 352 patients were included: 287 (81.5%) axSpA and 65 (18.5%) axPsA. No significant differences at baseline were observed between the two diseases for most of the characteristics. While HLA-B27 positivity was associated with axSpA (OR = 5.4; p < 0.001), peripheral manifestations were associated with axPsA (OR = 4.7; p < 0.001). The frequency of patients with axSpA and axPsA achieving ID/LDA after 6 and 12 months of bDMARDs was comparable: 53% versus 58%, p = 0.5; and 58% versus 60%, p = 0.9, respectively. Both diseases also presented similar clinical improvement. In axSpA and axPsA, male gender seemed to be associated with achieving LDA [OR at 12 months visit = 2.8 (p < 0.01) and 2.7 (p = 0.09)]. Conclusion: In clinical practice, patients with axSpA and axPsA present numerous similarities, including comparable medium-term clinical response to bDMARDs. Male gender could be a predictor of treatment response in both diseases.Keyword: axial spondyloarthritis, psoriatic arthritis, axial involvement, clinical characteristics.

7.
Reumatol. clín. (Barc.) ; 16(5,pt.2): 378-385, sept.-oct. 2020. tab, graf
Artigo em Espanhol | IBECS-Express | IBECS | ID: ibc-ET1-6650

RESUMO

OBJETIVOS: Emitir recomendaciones sobre aspectos prácticos de la monitorización de los niveles de fármacos biológicos que puedan ser de utilidad para reumatólogos. MÉTODOS: Se realizó una revisión sistemática de la literatura de estudios en los que se determinaron niveles de fármaco y de anticuerpos antifármaco en pacientes con artritis reumatoide o espondiloartritis para estudiar si podían predecir diferentes desenlaces. Con los resultados de la revisión un grupo de expertos discutió bajo qué circunstancias podría ser útil la solicitud de niveles de fármacos biológicos y sus anticuerpos, lo que se concretó en una serie de preguntas clínicas que fueron respondidas con la evidencia científica disponible y creándose algoritmos para facilitar la toma de decisiones. RESULTADOS: Se establece que la determinación de los niveles de fármaco puede ser especialmente útil en 2 situaciones clínicas, cuando hay fallo al tratamiento (primario o secundario) y en remisión mantenida. Se revisa también qué técnica de laboratorio y momento para tomar la muestra son los más adecuados para la medición, y se establecen recomendaciones sobre la interpretación de los niveles de fármaco y sobre factores a tener en cuenta (por ejemplo, índice de masa corporal y fármacos modificadores de la enfermedad). CONCLUSIONES: Se han elaborado algoritmos y establecido posibles pautas y directrices para solicitar niveles de fármaco y de anticuerpos antifármaco en pacientes con artritis reumatoide y espondiloartritis, basados en la evidencia, que pueden ayudar a la toma de decisiones clínicas


OBJECTIVES: Issue recommendations on practical aspects of the monitoring of levels of biological drugs that may be useful for rheumatologists. METHODS: We conducted a systematic review of studies in which drug and anti-drug antibody levels were determined in patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) to study whether they could predict different outcomes. In light of the results of the review, a group of experts discussed under what circumstances testing biological drug levels and their antibodies could be useful. The discussion resulted in a series of clinical questions that were answered with the scientific evidence collected, and in algorithms that facilitate decision making. RESULTS: It was established that the determination of drug levels can be especially useful in two clinical situations, on treatment failure (primary or secondary) and on sustained remission. It is also reviewed which laboratory technique and timing for sample drawing are the most suitable for the measurement. Recommendations are issued on the interpretation of drug levels and on factors to be taken into account (for example, body mass index and disease modifying drugs). CONCLUSIONS: Evidence-based algorithms and guidelines have been established to test drug levels and anti-drug antibodies in patients with RA and SpA, which can help clinical decision making

8.
Trials ; 21(1): 755, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867830

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is one of the leading chronic inflammatory rheumatism. First-line therapy with synthetic disease-modifying antirheumatic drugs (sDMARD) is insufficiently effective in 40% of cases and these patients are treated with biotherapies. The increased use of these drugs each year is becoming a public health issue with considerable economic burden. This cost is 20 times higher than that of sDMARD. However, among patients treated with biotherapies, clinical practice shows that about one third will not respond to the selected drug. In nonresponse cases, practitioners currently have no choice but to perform an empirical switching between different treatments, because no tool capable of predicting the response or nonresponse to these molecules is currently available. METHODS: The study is a prospective, phase III, controlled, multicenter, and randomized, single-blind (patient) clinical trial, including RA patients with a previous failure to anti-TNF therapies. The main objective is the analysis of the clinical and pharmacoeconomic impact after 6 months of treatment. Intervention arm: prescription of biotherapy (rituximab, adalimumab, abatacept) using SinnoTest® software, a prediction software based on proteomic biomarkers. Control arm: prescription of biotherapy based on current practice, without the SinnoTest® software (any biotherapy). In addition, a substudy will be carried out within this trial to generate a biobank and further analyze the proteomic profile of the patients and their modification throughout the study. DISCUSSION: This clinical trial study will be the first validation study of a biotherapy response prediction software, bringing personalized medicine into the management of RA. We expect that the findings from this study will bring several benefits for the patient and the Health Care System. TRIAL REGISTRATION: ClincalTrials.gov NCT04147026 . Registered on 31 October, 2019.

9.
Front Immunol ; 11: 1913, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973793

RESUMO

Background: TNF inhibitors (TNFis) are widely used for the treatment of rheumatoid arthritis (RA), although the response rates to this therapy in patients with RA remains heterogeneous and < 50% achieve remission (REM). Objective: To analyze baseline peripheral blood leukocytes profiles in order to search for biomarkers identifying patients who will most likely not achieve REM under TNFi treatment. Methods: A prospective bi-center pilot study including 98 RA patients treated with TNFis and followed-up during 6 months. Patients were classified according to DAS28 as follows: those who achieved REM (DAS28 ≤ 2.6) and those who did not (DAS28 > 2.6) at 6 months after starting TNFis. These rates were also assessed by simplified disease activity index (SDAI ≤ 3.3 and SDAI > 3.3, respectively). Peripheral blood immune cells were studied by flow cytometry before treatment initiation. Results: At 6 months, 61 or 80% of patients did not achieve REM by DAS28 or SDAI, respectively. Basal leukocyte profiles differed between REM vs. non-REM patients. Non-REM patients showed lower percentages of total and naïve B cells at baseline than REM subjects. A B lymphocyte/CD4+ lymphocyte ratio (BL/CD4 ratio) <0.2 clearly associated with a higher probability of non-REM status based on DAS28 at 6 months (OR = 9.2, p = 0.006). These data were confirmed when patient response was evaluated by SDAI index. Conclusion: Our results strongly suggest that BL/CD4 ratio could be considered as a useful biomarker for the early identification of non-remitters to TNFi in clinical practice.

10.
Ann Rheum Dis ; 79(12): 1659-1661, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32606046
11.
RMD Open ; 6(2)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32683326

RESUMO

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder with a global prevalence of approximately 0.5-1%. Patients with RA are at an increased risk of developing comorbidities (eg, cardiovascular disease, pulmonary disease, diabetes and depression). Despite this, there are limited recommendations for the management and implementation of associated comorbidities. This study aimed to identify good practice interventions in the care of RA and associated comorbidities. METHODS: A combination of primary research (180+ interviews with specialists across 12 European rheumatology centres) and secondary research (literature review of existing publications and guidelines/recommendations) were used to identify challenges in management and corresponding good practice interventions. Findings were prioritised and reviewed by a group of 18 rheumatology experts including rheumatologists, comorbidity experts, a patient representative and a highly specialised nurse. RESULTS: Challenges throughout the patient pathway (including delays in diagnosis and referral, shortage of rheumatologists, limited awareness of primary care professionals) and 18 good practice interventions were identified in the study. The expert group segmented and prioritised interventions according to three distinct stages of the disease: (1) suspected RA, (2) recent diagnosis of RA and (3) established RA. Examples of good practice interventions included enabling self-management (self-monitoring and disease management support, for example, lifestyle adaptations); early arthritis clinic; rapid access to care (online referral, triage, ultrasound-guided diagnosis); dedicated comorbidity specialists; enhanced communication with primary care (hotline, education sessions); and integrating patient registries into daily clinical practice. CONCLUSION: Learning from implementation of good practice interventions in centres across Europe provides an opportunity to more widely improved care for patients with RA and associated comorbidities.

12.
Rheumatology (Oxford) ; 59(10): 3081-3091, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32417912

RESUMO

OBJECTIVE: The protagonism of regulatory B cells seems to vary along the course of the disease in murine models of inflammatory conditions. Decreased numbers of circulating regulatory CD19+CD24hiCD38hi transitional (cTr) B cells have been described in patients with long-standing RA, thus our objective was to examine the frequency and evolution of cTr B cells in the peripheral blood of early RA (ERA) patients. METHODS: Freshly isolated peripheral blood mononuclear cells from 48 steroid- and DMARD-naïve ERA patients with a disease duration of <24 weeks and 48 healthy controls (HCs) were examined by flow cytometry. Co-cultures of isolated memory B cells were established with autologous T cells in the absence or presence of Tr B cells. RESULTS: As compared with HCs, ERA patients demonstrated an increased frequency of cTr B cells. cTr B cells of ERA patients and HCs displayed an anti-inflammatory cytokine profile and were able to downregulate T cell IFN-γ and IL-21 production, together with ACPA secretion in autologous B/T cell co-cultures. Basal frequencies of cTr B cells above the median value observed in HCs were associated with a good EULAR response to MTX at 12 months [relative risk 2.91 (95% CI 1.37, 6.47)]. A significant reduction of cTr B cells was observed 12 months after initiating MTX, when the cTr B cell frequency was no longer elevated but decreased, and this was independent of the degree of clinical response or the intake of prednisone. CONCLUSION: An increased frequency of regulatory cTr B cells is apparent in untreated ERA and the baseline cTr B cell frequency is associated with the clinical response to MTX at 12 months.

13.
J Clin Rheumatol ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015257

RESUMO

BACKGROUND: Using a machine learning approach, the study investigated if specific baseline characteristics could predict which psoriatic arthritis (PsA) patients may gain additional benefit from a starting dose of secukinumab 300 mg over 150 mg. We also report results from individual patient efficacy meta-analysis (IPEM) in 2049 PsA patients from the FUTURE 2 to 5 studies to evaluate the efficacy of secukinumab 300 mg, 150 mg with and without loading regimen versus placebo at week 16 on achievement of several clinically relevant difficult-to-achieve (higher hurdle) end points. METHODS: Machine learning employed Bayesian elastic net to analyze baseline data of 2148 PsA patients investigating 275 predictors. For IPEM, results were presented as difference in response rates versus placebo at week 16. RESULTS: Machine learning showed secukinumab 300 mg has additional benefits in patients who are anti-tumor necrosis factor-naive, treated with 1 prior anti-tumor necrosis factor agent, not receiving methotrexate, with enthesitis at baseline, and with shorter PsA disease duration. For IPEM, at week 16, all secukinumab doses had greater treatment effect (%) versus placebo for higher hurdle end points in the overall population and in all subgroups; 300-mg dose had greater treatment effect than 150 mg for all end points in overall population and most subgroups. CONCLUSIONS: Machine learning identified predictors for additional benefit of secukinumab 300 mg compared with 150 mg dose. Individual patient efficacy meta-analysis showed that secukinumab 300 mg provided greater improvements compared with 150 mg in higher hurdle efficacy end points in patients with active PsA in the overall population and most subgroups with various levels of baseline disease activity and psoriasis.

14.
Sci Rep ; 10(1): 3355, 2020 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-32098994

RESUMO

The major environmental risk factor for rheumatoid arthritis (RA) is smoking, which according to a widely accepted model induces protein citrullination in the lungs, triggering the production of anti-citrullinated protein antibodies (ACPA) and RA development. Nevertheless, some research findings do not fit this model. Therefore, we obtained six independent cohorts with 2253 RA patients for a detailed analysis of the association between smoking and RA autoantibodies. Our results showed a predominant association of smoking with the concurrent presence of the three antibodies: rheumatoid factor (RF), ACPA and anti-carbamylated protein antibodies (ACarPA) (3 Ab vs. 0 Ab: OR = 1.99, p = 2.5 × 10-8). Meta-analysis with previous data (4491 patients) confirmed the predominant association with the concurrent presence of the three antibodies (3 Ab vs. 0 Ab: OR = 2.00, p = 4.4 ×10-16) and revealed that smoking was exclusively associated with the presence of RF in patients with one or two antibodies (RF+1+2 vs. RF-0+1+2: OR = 1.32, p = 0.0002). In contrast, no specific association with ACPA or ACarPA was found. Therefore, these results showed the need to understand how smoking favors the concordance of RA specific antibodies and RF triggering, perhaps involving smoking-induced epitope spreading and other hypothesized mechanisms.


Assuntos
Anticorpos Anti-Proteína Citrulinada/sangue , Artrite Reumatoide/sangue , Epitopos/imunologia , Estudos Soroepidemiológicos , Anticorpos Anti-Proteína Citrulinada/imunologia , Artrite Reumatoide/complicações , Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Feminino , Cadeias HLA-DRB1/imunologia , Humanos , Testes Imunológicos , Masculino , Pacientes , Peptídeos Cíclicos/imunologia , Carbamilação de Proteínas/imunologia , Fator Reumatoide/sangue , Fator Reumatoide/imunologia , Fatores de Risco , Fumar/efeitos adversos
15.
Rheumatology (Oxford) ; 59(9): 2443-2447, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31953951

RESUMO

OBJECTIVES: To describe the frequency and causes for the presence of a halo sign on the ultrasound of patients without a diagnosis of GCA. METHODS: In total, 305 patients with temporal artery colour Doppler ultrasound showing the presence of halo sign (intima-media thickness ≥0.34 mm for temporal arteries [TAs] and ≥1 mm for axillary arteries) were included, and their medical records were reviewed. The clinical diagnosis based on the evolution of the patient over at least one year was established as the definitive diagnosis. RESULTS: Fourteen of the 305 (4.6%) patients included showed presence of the halo sign without final diagnosis of GCA: 12 patients in the TAs (86%), and two patients with isolated AAs involvement (14%). Their diagnoses were PMR (n = 4, 29%); atherosclerosis (n = 3, 21%); and non-Hodgkin lymphoma type T, osteomyelitis of the skull base, primary amyloidosis associated with multiple myeloma, granulomatosis with polyangiitis, neurosyphilis, urinary sepsis and narrow-angle glaucoma (n = 1 each, 7%). CONCLUSION: The percentage of halo signs on the ultrasound of patients without GCA is low, but it does exist. There are conditions that may also show the halo sign (true positive halo sign), and we must know these and always correlate the ultrasound findings with the patient's clinic records.

16.
Ann Rheum Dis ; 79(6): 685-699, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31969328

RESUMO

OBJECTIVES: To provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field. METHODS: An international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items. RESULTS: The task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high. CONCLUSIONS: These updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Sociedades Médicas , Medicamentos Sintéticos/uso terapêutico , Antirreumáticos/economia , Produtos Biológicos/economia , Consenso , Quimioterapia Combinada , Europa (Continente) , Humanos , Inibidores de Janus Quinases/uso terapêutico , Medicamentos Sintéticos/economia , Revisões Sistemáticas como Assunto , Fator de Necrose Tumoral alfa/antagonistas & inibidores
17.
Sci Rep ; 10(1): 1415, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996780

RESUMO

MUC5B rs35705950 (G/T) is strongly associated with idiopathic pulmonary fibrosis (IPF) and also contributes to the risk of interstitial lung disease (ILD) in rheumatoid arthritis (RA-ILD) and chronic hypersensitivity pneumonitis (CHP). Due to this, we evaluated the implication of MUC5B rs35705950 in antisynthetase syndrome (ASSD), a pathology characterised by a high ILD incidence. 160 patients with ASSD (142 with ILD associated with ASSD [ASSD-ILD+]), 232 with ILD unrelated to ASSD (comprising 161 IPF, 27 RA-ILD and 44 CHP) and 534 healthy controls were genotyped. MUC5B rs35705950 frequency did not significantly differ between ASSD-ILD+ patients and healthy controls nor when ASSD patients were stratified according to the presence/absence of anti Jo-1 antibodies or ILD. No significant differences in MUC5B rs35705950 were also observed in ASSD-ILD+ patients with a usual interstitial pneumonia (UIP) pattern when compared to those with a non-UIP pattern. However, a statistically significant decrease of MUC5B rs35705950 GT, TT and T frequencies in ASSD-ILD+ patients compared to patients with ILD unrelated to ASSD was observed. In summary, our study does not support a role of MUC5B rs35705950 in ASSD. It also indicates that there are genetic differences between ILD associated with and that unrelated to ASSD.


Assuntos
Doenças Pulmonares Intersticiais/genética , Mucina-5B/genética , Miosite/genética , Adulto , Feminino , Seguimentos , Humanos , Incidência , Doenças Pulmonares Intersticiais/epidemiologia , Masculino , Pessoa de Meia-Idade , Miosite/complicações , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética
18.
Reumatol Clin ; 16(5 Pt 2): 378-385, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30385295

RESUMO

OBJECTIVES: Issue recommendations on practical aspects of the monitoring of levels of biological drugs that may be useful for rheumatologists. METHODS: We conducted a systematic review of studies in which drug and anti-drug antibody levels were determined in patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) to study whether they could predict different outcomes. In light of the results of the review, a group of experts discussed under what circumstances testing biological drug levels and their antibodies could be useful. The discussion resulted in a series of clinical questions that were answered with the scientific evidence collected, and in algorithms that facilitate decision making. RESULTS: It was established that the determination of drug levels can be especially useful in two clinical situations, on treatment failure (primary or secondary) and on sustained remission. It is also reviewed which laboratory technique and timing for sample drawing are the most suitable for the measurement. Recommendations are issued on the interpretation of drug levels and on factors to be taken into account (for example, body mass index and disease modifying drugs). CONCLUSIONS: Evidence-based algorithms and guidelines have been established to test drug levels and anti-drug antibodies in patients with RA and SpA, which can help clinical decision making.

20.
Clin Exp Rheumatol ; 38(1): 82-87, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31573477

RESUMO

OBJECTIVES: To explore the remission concept in rheumatoid arthritis (RA) and the implications of the existing definitions when applied to clinical practice among rheumatologists with different profiles. METHODS: A qualitative study through focus groups was conducted. Three focus groups were organised from February to March 2016. Each group was composed of rheumatologists with extensive clinical experience with different profiles; experts in basic research (RBR), experts in imaging techniques research (RIR), and experts in clinical research (RCR). The data was collected with audio recording. Verbatim transcriptions of the audio files were made, and a subsequent reflexive thematic analysis assisted by ATLAS.ti (GmbH, Berlin, v. 7) software was performed. RESULTS: From the reflexive thematic analysis, three main themes were generated: (1) remission limitations, (2) instruments or measures to assess remission, and (3) a new definition of remission. Rheumatologists mentioned frequently that the following variables should be considered when developing a new remission definition: inflammatory activity, calprotectin, psychological variables, sex, disease stage, and sociocultural factors. Contrary to what could be expected, all groups acknowledged that their research field could contribute with domains for a gold standard remission instrument, but not in a hierarchical arrangement of importance. The dissonance existing in the entire remission evaluation process was outlined: remission in clinical practice versus remission in clinical trials, remission following the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean versus Musculoskeletal Ultrasound (US) remission, and remission from the rheumatologist's point of view versus the patient's point of view. CONCLUSIONS: Currently, rheumatologists would not accept a domain as more important than others in remission. Our suggestion is, not to generate a universal definition of remission - one that could cover all aspects - but rather to develop definitions of remission for the different settings that could be pondered by the patient's perspective.


Assuntos
Antirreumáticos , Artrite Reumatoide , Reumatologistas , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Humanos , Indução de Remissão , Índice de Gravidade de Doença , Terminologia como Assunto
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