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1.
Clin Exp Rheumatol ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31694743

RESUMO

OBJECTIVES: Interstitial lung disease (ILD) is a leading cause of mortality in patients with connective tissue diseases (CTD). Lung transplantation has become a viable option for patients with end-stage CTD-ILD. However, patients with CTD are often considered suboptimal candidates for lung transplantation because of concerns of worse outcomes. We assessed post-transplant survival of patients with CTD-ILD compared to patients with idiopathic pulmonary fibrosis (IPF). METHODS: Medical records of patients who underwent lung transplantation for CTD-ILD at a single referral centre for lung transplantation in Northern Spain between 1998 and 2018 were reviewed. This cohort was compared with patients with IPF (group-matched for age ±3.3 years, transplant year and use of basiliximab induction previous to transplant). Cumulative survival rates after transplantation were estimated by the Kaplan-Meier method and compared between groups using the log-rank test. RESULTS: We studied 26 patients with CTD-ILD and 26 patients with IPF. The underlying diseases of CTD-ILD patients were rheumatoid arthritis (n=9), scleroderma (n=6), Sjögren's syndrome (n=4), ANCA-associated vasculitis (n=3), anti-synthetase syndrome (n=2), and dermatomyositis, systemic lupus erythematosus (1 each). Baseline characteristics were similar in both groups. CTD-ILD patients experienced acute graft rejection less commonly than those with IPF (32.0% vs. 62.5%; p=0.032). However, a non-statistically significant increased frequency of chronic graft rejection was observed in CTD-ILD patients (20.0% vs. 8.3%; p=0.417). In this regard, the 5-year cumulative survival rates after transplantation was reduced in CTD-ILD (42.4% vs. 65.8%) but the difference did not achieve statistical significance (p=0.075). CONCLUSIONS: Long-term post-transplant survival in Northern Spanish patients with CTD-ILD is reduced compared with IPF.

2.
Clin Exp Rheumatol ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31694752

RESUMO

OBJECTIVES: To assess the plasma apolipoprotein B/apolipoprotein A1 ratio and its potential association with cardiovascular events (CVE) in patients with rheumatoid arthritis (RA). METHODS: A baseline analysis was made of the CARdiovascular in rheuMAtology Project (CARMA), a 10-year prospective study evaluating the presence of at least one CVE in 775 Spanish patients with RA. Of them, 29 had already experienced CVE prior to the inclusion in the study. We assessed the association between the elevation of the apoB/apoA1 ratio with the presence of CVE according to a logistic regression model for possible confounding factors. We also analysed the main parameters of activity of RA and parameters related to lipid metabolism. RA patients were classified according to treatment: patients treated with disease-modifying anti-rheumatic drugs without biologics and those undergoing biologic therapy (anti-TNF-α, anti-IL-6 receptor, and other biologic agents). RESULTS: The apoB/apoA1 ratio of patients who had experienced CVE was higher than that of patients without previous CVE (0.65 vs. 0.60). However, the difference between both subgroups did not reach statistical significance (p=0.197). It was also the case after the multivariate analysis [OR: 1.48 (95% CI: 0.15-14.4); p=0.735]. RA patients from the group with CVE were more commonly receiving lipid-lowering treatment with statins than those without CVE history (41.4% vs. 20%, p=0.005). High HAQ and high atherogenic index were significantly associated with the presence of CVE. There was no statistical association between the type of biologic therapy used in RA and the presence of CVE. CONCLUSIONS: No association between ApoB/apoA1 ratio and CVE was found at the baseline visit of patients with RA from the CARMA study.

3.
Arthritis Rheumatol ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31509349

RESUMO

OBJECTIVE: Pulmonary arterial hypertension (PAH), one of the major complications of systemic sclerosis (SSc), is a rare disease with unknown etiopathogenesis and non curative treatments. As PSGL-1-/- mice develop a spontaneous SSc-like syndrome, the objective of this work was to analyze whether they develop PAH and molecular mechanisms involved. METHODS: Doppler echocardiography was used to estimate pulmonary pressure; immunohistochemistry, to assess vascular remodeling; myography of dissected pulmonary artery rings, to analyze vascular reactivity. ELISA, to quantify the levels of AngII; Western blot, to measure AT1R, AT2R, eNOS and p-eNOS expression in lung lysates and Flow cytometry to determine cytokine production of immune cells and NO production by endothelial cells. In all cases, n = 4-8 mice per experimental group. RESULTS: PSGL-1-/- mice present lung vessel wall remodeling and reduced expression of pulmonary AT2R (>18-month-old female mice: WT 0.337±0.094 vs KO 0.189±0.072). With aging, PSGL-1-/- females have impaired up-regulation of ERα and develop lung vascular endothelial dysfunction coinciding with an increase in pulmonary AngII levels (WT 48.70±5.13 vs KO 78.02±28.09 pg/g lung tissue) and a decrease in eNOS phosphorylation, driving to reduced endothelial NO production. These events lead to reduction in PAAT/ET ratio in 33% of aged PSGL-1-/- females, indicating pulmonary hypertension. Importantly, we found expanded populations of IFN-γ-producing PSGL-1-/- T cells and B cells and reduced presence of regulatory T cells. CONCLUSION: PSGL-1 absence induces reduction of Treg, NO production and ERα expression and the increase of Angiotensin II in the lungs of female mice, favoring the development of PAH.

5.
Reumatol. clín. (Barc.) ; 15(4): 188-210, jul.-ago. 2019. tab, graf
Artigo em Espanhol | LILACS-Express | ID: ibc-ET1-3390

RESUMO

Objetivo: Actualizar las recomendaciones sobre osteoporosis (OP) de la Sociedad Española de Reumatología (SER) basadas en la mejor evidencia posible. Métodos: Se creó un panel formado por nueve reumatólogos expertos en OP previamente seleccionados por la SER mediante una convocatoria abierta. Las fases del trabajo fueron: identificación de las áreas claves para la actualización del consenso anterior, análisis y síntesis de la evidencia científica (utilizando los niveles de evidencia del SIGN) y formulación de recomendaciones a partir de esta evidencia y de técnicas de consenso. Resultados: Esta revisión de las recomendaciones comporta una actualización en la evaluación diagnóstica de la OP y de su tratamiento. Propone unos criterios para considerar alto riesgo de fractura y unas indicaciones para iniciar tratamiento. Las recomendaciones abordan también cuestiones relativas a la seguridad de los tratamientos y al manejo de situaciones especiales como las enfermedades inflamatorias y el tratamiento con glucocorticoides. Conclusiones: Se presenta la actualización de las recomendaciones SER sobre OP


Objective: To update the recommendations on osteoporosis (OP) of the Spanish Society of Rheumatology (SER) based on the best possible evidence. Methods: A panel of nine expert rheumatologists in OP was created, previously selected by the SER through an open call. The phases of the work were: identification of the key areas for updating the previous consensus, analysis and synthesis of the scientific evidence (using the SIGN levels of evidence) and formulation of recommendations based on this evidence and consensus techniques. Results: This revision of the recommendations implies an update in the diagnostic evaluation and treatment of OP. It proposes some criteria to consider the high risk of fracture and some indications to start treatment. The recommendations also address issues related to the safety of treatments and the management of special situations such as inflammatory diseases and treatment with glucocorticoids. Conclusions: We present an update of SER recommendations on OP

6.
Arthritis Rheumatol ; 71(12): 2081-2089, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31237427

RESUMO

OBJECTIVE: To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as a first-line biologic drug over 1 year of treatment in a large series of patients with refractory uveitis due to Behçet's disease (BD). METHODS: We conducted an open-label multicenter study of IFX versus ADA for BD-related uveitis refractory to conventional nonbiologic treatment. IFX or ADA was chosen as the first-line biologic agent based on physician and patient agreement. Patients received 3-5 mg/kg intravenous IFX at 0, 2, and 6 weeks and every 4-8 weeks thereafter, or 40 mg subcutaneous ADA every other week without a loading dose. Ocular parameters were compared between the 2 groups. RESULTS: The study included 177 patients (316 affected eyes), of whom 103 received IFX and 74 received ADA. There were no significant baseline differences between treatment groups in main demographic features, previous therapy, or ocular sign severity. After 1 year of therapy, we observed an improvement in all ocular parameters in both groups. However, patients receiving ADA had significantly better outcomes in some parameters, including improvement in anterior chamber inflammation (92.31% versus 78.18% for IFX; P = 0.06), improvement in vitritis (93.33% versus 78.95% for IFX; P = 0.04), and best-corrected visual acuity (mean ± SD 0.81 ± 0.26 versus 0.67 ± 0.34 for IFX; P = 0.001). A nonsignificant difference was seen for macular thickness (mean ± SD 250.62 ± 36.85 for ADA versus 264.89 ± 59.74 for IFX; P = 0.15), and improvement in retinal vasculitis was similar between the 2 groups (95% for ADA versus 97% for IFX; P = 0.28). The drug retention rate was higher in the ADA group (95.24% versus 84.95% for IFX; P = 0.042). CONCLUSION: Although both IFX and ADA are efficacious in refractory BD-related uveitis, ADA appears to be associated with better outcomes than IFX after 1 year of follow-up.

7.
Med. clín (Ed. impr.) ; 152(9): 353-360, mayo 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-183661

RESUMO

La ruta de señalización de las proteínas de la familia Janus cinasa (JAK) está implicada en la patogenia de muchas enfermedades inflamatorias y autoinmunitarias, como la artritis reumatoide (AR), la psoriasis y la enfermedad inflamatoria intestinal. Una gran cantidad de citocinas implicadas en el desarrollo de estas enfermedades utilizan esta vía de señalización para transducir señales intracelulares. En los últimos años, la aparición de los inhibidores de las proteínas JAK (jakinibs) ha demostrado que los fármacos relacionados con esta ruta patogénica pueden tener gran aplicabilidad clínica. Tofacitinib y baricitinib, primeros jakinibs aprobados para el tratamiento de la AR, están en estudio para el tratamiento de otras enfermedades autoinmunitarias. Asimismo, otros jakinibs se encuentran en diferentes fases de desarrollo. En este trabajo se revisan los principales aspectos en cuanto a eficacia, interacciones farmacológicas y seguridad tanto de los jakinibs clásicos como de los de nueva generación


The Janus kinase (JAK) pathway is implicated in the pathogenesis of many inflammatory and autoimmune diseases including rheumatoid arthritis (RA), psoriasis, and inflammatory bowel disease. There are a lot of proinflammatory cytokines involved in such diseases using this pathway to transduce intracellular signals. In the last years, JAK inhibitors (jakinibs) have appeared with a great success, showing that these kinds of drugs have a great applicability in clinical practice. Tofacitinib and baricitinib, the first jakinibs approved for the treatment of RA, are being investigated also for treating other autoimmune systemic diseases. Likewise, other jakinibs are in several phases of development. This review analyses the safety and clinical efficacy of the jakinibs, starting with the classics and continuing with next-generation jakinibs


Assuntos
Humanos , Inibidores de Janus Quinases/administração & dosagem , Proteínas Inibidoras de STAT Ativados/administração & dosagem , Doenças do Sistema Imunitário/tratamento farmacológico
8.
Artigo em Inglês | MEDLINE | ID: mdl-31033231

RESUMO

OBJECTIVE: To evaluate the impact of comorbidities on the physical function in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS: Cross-sectional analysis of the baseline visit from the CARMA study. Multivariate models with physical function as the dependent variable (BASFI and HAQ for AS and PsA, respectively) were performed. INDEPENDENT VARIABLES: A proxy for the Charlson Comorbidity Index (CCIp) (range: 0-27); sociodemographic data; disease activity (ESR and BASDAI in AS; DAS28-ESR in PsA); disease duration; radiographic damage and treatments. Results were reported as ß-coefficients, 95% confidence intervals [95%CI] and p-values. RESULTS: We included 738 patients with AS and 721 with PsA; 21% of them had more than one comorbidity. Comorbidity burden (CCIp) was independently associated with worse adjusted physical function in patients with PsA (ß: 0.11). Also, female sex (ß: 0.14), disease duration (ß: 0.01), disease activity (DAS28-ESR, ß: 0.19), NSAIDs (ß: 0.09), glucocorticoids (ß: 0.11) and biologics (ß: 0.15) were associated with worse function in patients with PsA. A higher educational level was associated with less disability (ß: -0.14). In patients with AS, age (ß: 0.03), disease activity (BASDAI; ß: 0.81), radiographic damage (ß: 0.61) and the use of biologics (ß: 0.51) were independently associated with worse function on multivariate analyses, but CCIp was not. CONCLUSION: The presence of comorbidities in patients with PsA is independently associated with worse physical function. The detection and control of the comorbidities may yield an integral management of the disease. This article is protected by copyright. All rights reserved.

9.
Biochem Pharmacol ; 165: 230-239, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31034796

RESUMO

Giant cell arteritis (GCA) is the most common form of vasculitis in adults. Cranial manifestations are typical clinical features of this vasculitis. Sometimes the presenting symptoms are nonspecific and, in some cases, large-vessel involvement may prevail. Polymyalgia rheumatica is a frequent manifestation that in some cases may be the presenting symptom of GCA. Visual complications, in particular the risk of blindness, constitute the most feared manifestations of GCA. Prompt recognition of this vasculitis is required to avoid irreversible complications. Prednisone/prednisolone at a dose of 40-60 mg/day is the cornerstone therapy in GCA. Glucocorticoids lead to rapid improvement of symptoms and may reduce the risk of irreversible visual loss. However, relapses are common when the prednisone dose is tapered. Therefore, additional therapies are required in relapsing GCA or when a rapid reduction of glucocorticoids is needed. The most widely used conventional immunosuppressive drug is methotrexate Adjunctive treatment with methotrexate may decrease the risk of relapses and reduce glucocorticoid exposure. However, comprehensive reviews indicate that the efficacy of methotrexate in GCA is modest. The experience with other conventional immunosuppressive drugs in GCA patients is scarce. In some cases, the new biologic agents are required. Among them, the most frequently used is the recombinant humanized anti-IL-6 receptor antibody tocilizumab. It improves clinical symptoms, reduce the cumulative prednisone dose and the frequency of relapses in GCA patients. However, anti-tumor necrosis factor-α therapy is not useful in GCA. Promising results on other biologic agents, such as abatacept, ustekinumab or anakinra, require further confirmatory studies.

10.
J Clin Densitom ; 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30910402

RESUMO

Reduction in cortical bone mineral density at diaphysis of metacarpal bones of the hand, evaluated by dual X-ray radiogrammetry, has a bad prognostic value in patients with early arthritis. Nevertheless, this technique is hardly accessible in clinical practice. By contrast, evaluation of cortical bone mineral density at that location has not been previously assessed by conventional dual X-ray absorptiometry. The aim of this study is to evaluate the reproducibility of bone mineral density measurements at diaphysis of metacarpal bones using conventional dual X-ray densitometry in a population of healthy volunteers and patients with early arthritis. Nondominant hand dual X-ray densitometry was performed at three consecutive times with complete hand replacement in 27 subjects: 10 early arthritis and 17 healthy volunteers. Three different evaluators analyzed the 3 measurements of second to fourth metacarpal bones. To assess the reproducibility and accuracy of the measurements, intra- and interobserver agreement degrees, intra- and interclass correlation coefficients, smallest difference detectable assessment, and Bland Altman graphs were calculated. The coefficients of variation obtained for the different metacarpal evaluations were 2.25%, 2.91%, 2.85%, and 2.07% for metacarpal-2, metacarpal-3, metacarpal-4, and mean metacarpal-second to fourth, respectively, with a smallest difference detectable of 0.028, 0.034, 0.028, and 0.03 g/cm2, respectively. The mean intra- and interobserver correlation coefficients between of metacarpal second to fourth were 0.990 (95% confidence interval [CI]: 0.982-0.995) and 0.995 (95% CI: 0.991-0.997), respectively. As expected, women had lower bone mineral density at metacarpal bones, especially after menopause. The results obtained in this study show an excellent reproducibility of bone mineral density measurements at diaphysis of metacarpal bones of the hand, measured by conventional dual X-ray densitometry, in a mixed population of healthy subjects and patients with early arthritis. This is of great interest for longitudinal studies in patients with early arthritis.

11.
Expert Opin Biol Ther ; 19(4): 273-286, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30827128

RESUMO

INTRODUCTION: Adult-onset Still´s disease (AOSD) is a systemic inflammatory condition that affects mainly young people. The clinical course consists of two distinctive patterns: one with a predominance of systemic symptoms and another manifested by progressive chronic polyarthritis. Glucocorticoids remain the mainstay in the treatment of AOSD. However, biologic therapies are often required to achieve clinical remission and allow glucocorticoid discontinuation. Areas covered: The review summarizes the main retrospective and prospective studies, and case series on the use of the anti-interleukin (IL)-6 receptor tocilizumab in AOSD. Expert opinion: Since IL-6 serum levels are highly increased in both active systemic and polyarticular phenotypes, IL-6 blockade was considered to be a plausible therapeutic option for the management of AOSD. Tocilizumab, the only anti-IL-6-receptor antagonist currently available for AOSD, has proved to be effective for the management of refractory AOSD patients, including those with life-threatening complications. Nevertheless, there are some reports describing patients who are refractory to any therapy. Future research should focus on the identification of prognostic biomarkers that help us to tailor an individualized treatment for each type of patient and in the search of new disease activity indices that help us to monitor the response to the therapy more closely.

12.
Biochem Pharmacol ; 165: 221-229, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30904473

RESUMO

Polymyalgia rheumatica (PMR) is an inflammatory disease characterized by bilateral pain involving predominantly the shoulders and proximal aspects of the arms and less commonly the neck and the pelvic girdle. This review discusses briefly the main epidemiological data and clinical features of this condition. Especial attention is paid in the management of the disease. For this reason, both the classic management and the impact of new therapies are discussed in depth. In general, patients with PMR experience a rapid response to 12.5-25 mg/prednisone/day in less than a week. Patients with poor response to glucocorticoids or with relapsing disease require other therapies aimed mainly to spare glucocorticoids. Among them, methotrexate is the most commonly used. Nevertheless, different studies indicate that this agent yields only a modest effect. Biologic therapies against the main cytokines involved in the pathogenesis of the disease have been used in refractory patients. However, randomized controlled trials do not support the use of anti-tumor necrosis factor agents in PMR. In contrast, several case series and retrospective studies highlight the efficacy of the anti-interleukin-6 receptor tocilizumab in PMR. Nonetheless, controlled trials are needed to fully establish the beneficial effect of this agent. The potential favorable effect of the Janus-kinase inhibitors and new anti-interleukin-6 antagonists remains to be determined.

13.
Sci Rep ; 9(1): 2777, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30808881

RESUMO

Behçet's disease (BD) is an immune-mediated systemic disorder with a well-established genetic base. In a previous study, using a next generation sequencing approach, we found many rare variants and some functional polymorphisms in genes related to autoinflammatory syndromes (AID): CECR1, MEFV, MVK, NLRP3, NOD2, PSTPIP1 and TNFRSF1A in our BD cohort. Our strategy did not allow us to establish either number of patients with variants, proportion of individuals accumulating them or relationship with other genetic factors. With the goal to answer these questions, the individual samples were sequenced. Additionally, three functional polymorphisms: NLRP3 p.Gln703Lys, NOD2 p.Arg702Trp and p.Val955Ile were genotyped using TaqMan assays. A total of 98 patients (27.6%) carried at least one rare variant and 13 of them (3.7%) accumulated two or three. Functional regression model analysis suggests epistatic interaction between B51 and MEFV (P = 0.003). A suggestive protective association of the minor allele of NOD2 p.Arg702Trp (P = 0.01) was found in both, B51 positive and negative individuals. Therefore, a high percentage of patients with BD have rare variants in AID genes. Our results suggest that the association of MEFV with BD could be modulated by the HLA molecules; whereas the protective effect of NOD2 p.Arg702Trp would be independent of HLA.

14.
Clin Exp Rheumatol ; 37(5): 774-782, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30789151

RESUMO

OBJECTIVES: Cardiovascular (CV) disease is one of the main causes of morbi-mortality in spondyloarthritis (SpA), partially explained by traditional CV risk factors. Information on lipoprotein(a) [Lp(a)], a non-conventional risk factor, in SpA is scarce. In this study we assessed the prevalence of hyperlipoproteinaemia(a) in SpA patients and analysed the possible related factors. METHODS: A baseline analysis was made of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients and controls included in the CARMA project (CARdiovascular in RheuMAtology), a 10-year prospective study evaluating the risk of CV events in chronic inflammatory rheumatic diseases. A multivariate logistic regression model was performed using hyperlipoproteinaemia(a) (Lp(a) >50 mg/dl) as a dependent variable and adjusting for confounding factors. RESULTS: 19.2% (95% CI: 16.80-22.05) of the SpA patients [20.7% (95% CI: 16.91-24.82) of those with AS and 17.7% (95% CI: 14.15-21.75) of those with PsA] and 16.7% (95% CI: 13.23-20.86) of the controls had hyperlipoproteinaemia(a) (p=0.326). Adjusting for age and sex, SpA patients were more likely to have hyperlipoproteinaemia(a) than controls (OR: 1.43, 95%CI: 1.00-2.04; p=0.05), especially those with AS (OR: 1.81, 95%CI: 1.18-2.77; p=0.007). In the adjusted model, apolipoprotein B in all patients, non-steroidal anti-inflammatory drugs in AS, and female sex in PsA, were associated with hyperlipoproteinaemia(a). No disease-specific factors associated with hyperlipoproteinaemia(a) were identified. CONCLUSIONS: SpA patients show a moderately increased risk of hyperlipoproteinaemia(a) compared to controls, especially those with AS. Lp(a) determination may be of interest to improve the CV risk assessment in SpA patients.


Assuntos
Hiperlipoproteinemias , Espondilartrite , Artrite Psoriásica , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Hiperlipoproteinemias/epidemiologia , Masculino , Estudos Prospectivos , Fatores de Risco , Espondilartrite/sangue , Espondilartrite/epidemiologia
15.
Clin Exp Rheumatol ; 37(5): 731-739, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30620291

RESUMO

OBJECTIVES: To determine the incidence and risk factors of first cardiovascular event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD). METHODS: Analysis of data after 2.5 years of follow-up from the prospective study CARMA project, that includes patients with CIRD [rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA)] and matched individuals without CIRD from 67 hospitals in Spain. CVE cumulative incidence per 1000 patients was calculated after 2.5 years from the start of the project. Weibull proportional hazard model was used to calculate hazard ratio (HR) and 95% confidence interval (95% CI) of the risk factors. RESULTS: 2595 (89.1%) patients completed the 2.5 years of follow-up visit. Cumulative incidence of CVE in patients with CIRD was 15.30 cases per 1000 patients (95% CI: 12.93-17.67), being higher in the subgroup with AS; 22.03 (95% CI: 11.01-33.04). Patients with AS (HR: 4.11; 95% CI: 1.07-15.79), those with older age (HR: 1.09; 95% CI: 1.05-1.13), systolic hypertension (HR: 1.02; 95% CI: 1.00-1.04) and long duration of the disease (HR: 1.07; 95% CI: 1.03-1.12) were at higher risk of first CVE during the 2.5 years of follow-up. In contrast, female gender was a protective factor (HR: 0.43; 95% CI: 0.18-1.00). CONCLUSIONS: Among CIRD patients prospectively followed-up at rheumatology outpatient clinics, those with AS show higher risk of first CVE. Besides cardiovascular risk factors, such as hypertension, being a man and older as well as having a long disease duration increase the risk of CVE in patients with CIRD.


Assuntos
Artrite Psoriásica/epidemiologia , Artrite Reumatoide/epidemiologia , Doenças Cardiovasculares/epidemiologia , Espondilite Anquilosante/epidemiologia , Idoso , Comorbidade , Feminino , Humanos , Incidência , Masculino , Estudos Prospectivos , Doenças Reumáticas/epidemiologia , Fatores de Risco , Espanha/epidemiologia
16.
Semin Arthritis Rheum ; 49(1): 126-135, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30655091

RESUMO

OBJECTIVE: Tocilizumab (TCZ) has shown efficacy in clinical trials on giant cell arteritis (GCA). Real-world data are scarce. Our objective was to assess efficacy and safety of TCZ in unselected patients with GCA in clinical practice Methods: Observational, open-label multicenter study from 40 national referral centers of GCA patients treated with TCZ due to inefficacy or adverse events of previous therapy. Outcomes variables were improvement of clinical features, acute phase reactants, glucocorticoid-sparing effect, prolonged remission and relapses. A comparative study was performed: (a) TCZ route (SC vs. IV); (b) GCA duration (≤6 vs. >6 months); (c) serious infections (with or without); (d) ≤15 vs. >15 mg/day at TCZ onset. RESULTS: 134 patients; mean age, 73.0 ± 8.8 years. TCZ was started after a median [IQR] time from GCA diagnosis of 13.5 [5.0-33.5] months. Ninety-eight (73.1%) patients had received immunosuppressive agents. After 1 month of TCZ 93.9% experienced clinical improvement. Reduction of CRP from 1.7 [0.4-3.2] to 0.11 [0.05-0.5] mg/dL (p < 0.0001), ESR from 33 [14.5-61] to 6 [2-12] mm/1st hour (p < 0.0001) and decrease in patients with anemia from 16.4% to 3.8% (p < 0.0001) were observed. Regardless of administration route or disease duration, clinical improvement leading to remission at 6, 12, 18, 24 months was observed in 55.5%, 70.4%, 69.2% and 90% of patients. Most relevant adverse side-effect was serious infections (10.6/100 patients-year), associated with higher doses of prednisone during the first three months of therapy. CONCLUSION: In clinical practice, TCZ yields a rapid and maintained improvement of refractory GCA. Serious infections appear to be higher than in clinical trials.

17.
Clin Exp Rheumatol ; 37(4): 615-622, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30620289

RESUMO

OBJECTIVES: Reconstitution of B-cells after their therapeutic depletion with rituximab mimics the ontogeny of the B-cell linage in patients with rheumatoid arthritis. However, little is known about the effects of multiple cycles of treatment on the repletion kinetics and their long-lasting effects on the B-cell compartment. We therefore compared the recovery capacity of the B cell subpopulations between patients who experienced their first cycle of rituximab and those who experienced successive cycles. METHODS: The distribution of the different B-cell subsets was characterised by multiparametric flow cytometry in the peripheral blood of 29 patients in the first rituximab course (naïve cycles) and 40 patients in successive cycles. Samples were obtained at baseline and at 3, 6, and 8 months of each cycle. RESULTS: The baseline percentage of B-cell subsets was similar among successive cycles. Therefore, successive cycles were grouped for comparison with naïve cycles. Patients in naïve cycles had higher percentages at baseline of both total and memory B-cells. However, the recovery of the different B-cell subsets was similar between naïve and successive cycles. In naïve patients the percentage of transitional B-cells significantly correlated with disease activity at baseline. CONCLUSIONS: Rituximab induces a long-term reshape of the B-cell compartment while multiple cycles of rituximab do not induce cumulative effects on B-cell subpopulations. Transitional B-cells seem to be associated with higher disease activity, although further studies are needed to determine if they can be used as a biomarker to predict the need for rituximab retreatment.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide , Rituximab/uso terapêutico , Anticorpos Monoclonais Murinos , Artrite Reumatoide/imunologia , Linfócitos B , Humanos
18.
Med Clin (Barc) ; 152(9): 353-360, 2019 May 03.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30527218

RESUMO

The Janus kinase (JAK) pathway is implicated in the pathogenesis of many inflammatory and autoimmune diseases including rheumatoid arthritis (RA), psoriasis, and inflammatory bowel disease. There are a lot of proinflammatory cytokines involved in such diseases using this pathway to transduce intracellular signals. In the last years, JAK inhibitors (jakinibs) have appeared with a great success, showing that these kinds of drugs have a great applicability in clinical practice. Tofacitinib and baricitinib, the first jakinibs approved for the treatment of RA, are being investigated also for treating other autoimmune systemic diseases. Likewise, other jakinibs are in several phases of development. This review analyses the safety and clinical efficacy of the jakinibs, starting with the classics and continuing with next-generation jakinibs.

19.
Ann Rheum Dis ; 78(3)2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30552173

RESUMO

OBJECTIVE: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA. METHODS: We performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case-control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA. RESULTS: We identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDR<0.05). From these, the glycosaminoglycan (GAG) metabolism pathway was confirmed to be disease-specific after comparing the PsA cohort with the cohorts of patients with PsC and RA. Finally, we identified candidate drug targets in the GAG metabolism pathway as well as new PsA indications for approved drugs. CONCLUSION: These findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.

20.
Artigo em Inglês | MEDLINE | ID: mdl-30513026

RESUMO

INTRODUCTION: Giant cell arteritis is a vasculitis of large and middle-sized arteries that affects individuals older than 50 years. Although glucocorticoids remain the mainstay in the treatment of this vasculitis, other drugs are often required to achieve clinical remission and allow glucocorticoid discontinuation. Areas covered: The review summarizes the main biologic therapies used for the managements of GCA. Expert commentary: Although several biologic agents have been used in patients with GCA, the only biologic agent currently approved for this purpose is the recombinant humanized anti-IL-6 receptor antibody: tocilizumab. It has demonstrated efficacy to improve clinical symptoms, decrease the cumulative prednisone dose and reduce the frequency of relapses in clinical trials and real-life studies on patients with GCA. A trial showed that abatacept may be useful to maintain remission in GCA patients. An open-label study suggested that ustekinumab could be useful for the treatment of patients with refractory GCA. However, further studies are required to confirm if both abatacept and ustekinumab are useful as an adjunctive therapy to reduce relapses or as a glucocorticoid-sparing agent in GCA. Anakinra has been successfully used in a few patients with refractory GCA. In contrast, anti-tumor necrosis factor-α therapy yielded disappointing results in GCA.

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