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OBJECTIVES: To compare the safety of Janus kinase inhibitors (JAKi) with that of tumour necrosis factor inhibitors (TNFi) and determine drug persistence among patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: We analysed data from patients included in BIOBADASER 3.0 and treated with JAKi or TNFi from 2015 to 2023 and estimated the incidence rate ratio (IRR) of adverse events and persistence. RESULTS: A total of 6826 patients were included. Of these, 52% had RA, 25% psoriatic arthritis and 23% axial SpA. Treatment was with TNFi in 86%. The mean duration of treatment was 2.2±2.0 years with TNFi versus 1.8±1.5 with JAKi. JAKis were prescribed in older patients with longer term disease, greater comorbidity and later treatment lines and more frequently as monotherapy. The IRR of all infections and gastrointestinal events was higher among patients with RA treated with JAKi. Drug persistence at 1, 2 and 3 years was 69%, 55% and 45% for TNFi and 68%, 54% and 45% for JAKi. Multivariate regression models showed a lower probability of discontinuation for JAKi (HR=0.85; 95% CI 0.78-0.92) and concomitant conventional synthetic disease-modifying antirheumatic drugs (HR=0.90; 95% CI 0.84-0.96). The risk of discontinuation increased with glucocorticoids, comorbidities, greater disease activity and later treatment lines. CONCLUSIONS: Infections, herpes zoster and gastrointestinal adverse events in patients with RA tended to be more frequent with JAKi. However, prognosis was poor in patients receiving JAKi. Persistence was similar for TNFi and JAKi, although factors associated with discontinuation differed by diagnostic group.
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OBJECTIVE: The persistence of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs(DMARDs) in monotherapy versus in combination with conventional synthetic (cs) DMARDs is still a controversial topic in rheumatic diseases. To clarify this issue, the retention of the initial treatment strategy of b/tsDMARD in combination with csDMARD versus monotherapy in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients under real-life conditions was evaluated. Factors associated with maintenance of the initial strategy were analysed. METHODS: Nested cohort study within the Spanish BIOBADASER III registry. Bivariate comparisons and multivariate Cox proportional hazards models were used for the analyses. RESULTS: A total of 2521 patients were included in the study. In the multivariate model, the initial strategy of combination therapy was associated with shorter persistence in patients with RA (hazard ratio [HR] 1.58;95% confidence interval [CI] 1.00-2.50; p = .049), PsA (HR 2.48; 95% CI 1.65-3.72) and AS (HR 16.77; 95% CI 7.37-38.16; p < .001), regardless of sex, time of disease progression, baseline disease activity, glucocorticoid use or type of b/tsDMARD. Overall, the combination strategy was associated with an increased incidence of adverse events (incidence rate ratio [IRR] 1.13; 95% CI 1.05-1.21). CONCLUSIONS: In this real-life study, the strategy of combining a b/tsDMARD with a csDMARD is associated with lower persistence and worse safety profile compared to monotherapy in RA and especially in PsA and AS, suggesting that combination therapy should be rethought as first choice in RA patients, but especially in PsA and AS patients.
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Antirreumáticos , Artritis Psoriásica , Artritis Reumatoide , Espondilitis Anquilosante , Humanos , Artritis Psoriásica/tratamiento farmacológico , Estudios de Cohortes , Artritis Reumatoide/tratamiento farmacológico , Antirreumáticos/uso terapéutico , Espondilitis Anquilosante/tratamiento farmacológico , Quimioterapia CombinadaRESUMEN
OBJECTIVE: To assess the efficacy of abatacept (ABA) in RA patients with interstitial lung disease (ILD) (RA-ILD). METHODS: This was an observational, multicentre study of RA-ILD patients treated with at least one dose of ABA. ILD was diagnosed by high-resolution CT (HRCT). We analysed the following variables at baseline (ABA initiation), 12 months and at the end of the follow-up: Modified Medical Research Council (MMRC) scale (1-point change), forced vital capacity (FVC) or diffusion lung capacity for carbon monoxide (DLCO) (improvement or worsening ≥10%), HRCT, DAS on 28 joints evaluated using the ESR (DAS28ESR) and CS-sparing effect. RESULTS: We studied 263 RA-ILD patients [150 women/113 men; mean (s.d.) age 64.6 (10) years]. At baseline, they had a median duration of ILD of 1 (interquartile range 0.25-3.44) years, moderate or severe degree of dyspnoea (MMRC grade 2, 3 or 4) (40.3%), FVC (% of the predicted) mean (s.d.) 85.9 (21.8)%, DLCO (% of the predicted) 65.7 (18.3) and DAS28ESR 4.5 (1.5). The ILD patterns were: usual interstitial pneumonia (UIP) (40.3%), non-specific interstitial pneumonia (NSIP) (31.9%) and others (27.8%). ABA was prescribed at standard dose, i.v. (25.5%) or s.c. (74.5%). After a median follow-up of 12 (6-36) months the following variables did not show worsening: dyspnoea (MMRC) (91.9%); FVC (87.7%); DLCO (90.6%); and chest HRCT (76.6%). A significant improvement of DAS28ESR from 4.5 (1.5) to 3.1 (1.3) at the end of follow-up (P < 0.001) and a CS-sparing effect from a median 7.5 (5-10) to 5 (2.5-7.5) mg/day at the end of follow-up (P < 0.001) was also observed. ABA was withdrawn in 62 (23.6%) patients due to adverse events (n = 30), articular inefficacy (n = 27), ILD worsening (n = 3) and other causes (n = 2). CONCLUSION: ABA may be an effective and safe treatment for patients with RA-ILD.
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Abatacept/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/complicaciones , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Abatacept/efectos adversos , Antirreumáticos/efectos adversos , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/etiología , Masculino , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
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.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Enfermedades Cardiovasculares , Apolipoproteína A-I , Apolipoproteínas B , Humanos , Estudios Prospectivos , Factor de Necrosis Tumoral alfa/uso terapéuticoRESUMEN
The objective of our study was to standardize magnetic resonance imaging (MRI) assessment of spine and sacroiliac joints in patients with axial spondyloarthritis (axSpA) and/or inflammatory spinal pain, by creating checklists and templates based on the opinions of rheumatologists and radiologists. A scientific committee developed a series of questionnaires with multiple items regarding MRI in patients with axial inflammatory pain and/or axSpA. Then an expert panel of rheumatologists and radiologists rated all items in a 9-point Likert scale. Finally, the scientific committee and the expert panel met to create the definitive documents. Several definitive checklists and templates were generated for rheumatologist-requested MRI and for radiologist-requested MRI reports of sacroiliac joint and spinal examinations. A technical requirement protocol was also agreed on. Our results could be useful in increasing understanding between rheumatologists and radiologists regarding MRI in axSpA diagnosis and follow-up.
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Lista de Verificación , Imagen por Resonancia Magnética , Articulación Sacroiliaca/diagnóstico por imagen , Columna Vertebral/diagnóstico por imagen , Espondiloartritis/diagnóstico por imagen , Humanos , Sacroileítis/diagnóstico por imagen , Encuestas y CuestionariosRESUMEN
BACKGROUND: The IL-6 -174G/C genetic variant has recently been associated with the clinical response to etanercept therapy in rheumatoid arthritis (RA) patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the antitumor necrosis factor (anti-TNF) treatment outcome in RA. MATERIALS AND METHODS: Our study population was composed of 199 Spanish patients with RA receiving anti-TNF therapy. The IL-6 -174G/C (rs1800795) genetic variant was genotyped using the TaqMan allelic discrimination technology. Patients were classified, according to the European League Against Rheumatism (EULAR) criteria, as responders (good and moderate response) and nonresponders at 6, 12, 18, and 24 months after the first infusion. RESULTS: The -174*G allele was significantly associated with a good or moderate EULAR response at 12 [P=0.015, odds ratio (OR)=2.93, 95% confidence interval (CI) 1.29-6.70], 18 (P=4.54E-03, OR=5.17, 95% CI 1.80-14.85), and 24 months (P=4.54E-03, OR=14.86, 95% CI 2.91-75.91). A meta-analysis combining these data with the results from a previous study confirmed this association (P=1.89E-02, OR=1.80, 95% CI 1.13-2.87, at 12 months). CONCLUSION: Our results support the role of the -174G/C IL-6 polymorphism as a genetic marker of responsiveness to anti-TNF therapy.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Inmunoglobulina G/uso terapéutico , Interleucina-6/genética , Regiones Promotoras Genéticas , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab , Adulto , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/administración & dosificación , Artritis Reumatoide/genética , Citosina , Etanercept , Femenino , Marcadores Genéticos , Genotipo , Guanina , Humanos , Inmunoglobulina G/administración & dosificación , Infliximab , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Receptores del Factor de Necrosis Tumoral/administración & dosificación , Reproducibilidad de los Resultados , Resultado del TratamientoRESUMEN
INTRODUCTION: The management of specific clinical scenarios is not adequately addressed in national and international guidelines for axial spondyloarthritis (axSpA). Expert opinions could serve as a valuable complement to these documents. METHODS: Seven expert rheumatologists identified controversial areas or gaps of current recommendations for the management of patients with axSpA. A systematic literature review (SLR) was performed to analyze the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional synthetic, biologic and targeted synthetic disease-modifying antirheumatic drugs (csDMARDs, b/tsDMARDs) in axSpA regarding controversial areas or gaps. In a nominal group meeting, the results of the SLR were discussed and a set of statements were proposed. A Delphi process inviting 150 rheumatologists was followed to define the final statements. Agreement was defined as if at least 70% of the participants voted ≥ 7 (from 1, totally disagree, to 10, totally agree). RESULTS: Three overarching principles and 17 recommendations were generated. All reached agreement. According to them, axSpA care should be holistic and individualized, taking into account objective findings, comorbidities, and patients' opinions and preferences. Integrating imaging and clinical assessment with biomarker analysis could also help in decision-making. Connected to treatments, in refractory enthesitis, b/tsDMARDs are recommended. If active peripheral arthritis, csDMARD might be considered before b/tsDMARDs. The presence of significant structural damage, long disease duration, or HLA-B27-negative status do not contraindicate for the use of b/tsDMARDs. CONCLUSIONS: These recommendations are intended to complement guidelines by helping health professionals address and manage specific groups of patients, particular clinical scenarios, and gaps in axSpA.
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Background: To evaluate gender differences in disease activity and health status (HS) in patients with radiographic axial spondyloarthritis (r-axSpA)/ankylosing spondylitis (AS). Methods: Ancillary analysis of the MIDAS study, an observational, non-interventional, cross-sectional and retrospective multicenter nationwide study to assess disease activity and its relationship with HS in clinical practice. Adult patients with AS diagnosis, fulfilling ASAS and modified New York criteria, treated for ≥3 months upon study inclusion according to clinical practice were included. The primary outcome was "disease control" assessed by the percentage of patients in remission and low disease activity (BASDAI and ASDAS-CRP scores). HS was evaluated using the ASAS health index (ASAS-HI). Patients' responses and characteristics were analyzed by gender. Results: We analyzed 313 patients with AS, 237 (75.7%) males and 76 (24.3%) females. A total of 202 (64.5%) patients had adequate disease control (BASDAI < 4); 69.2% of males [mean (SD) BASDAI 2.9 (2.1)] and 50.0% of females [mean (SD) BASDAI 3.8 (2.4); p = 0.01]. According to ASDAS-CRP, 57.5% of patients were adequately controlled (ASDAS-ID +ASDAS-LDA); 138 (58.2%) males and 42 (55.3%) females. The mean (SD) ASDAS-CRP was 1.9 (1.1); being 1.9 (1.0) in males and 2.0 (1.1) in females. Overall, the impact of AS on HS was low to moderate [mean (SD) ASAS-HI 5.8 (4.4)]; being 5.5 (4.4) for males and 6.8 (4.2) for females (p = 0.02). Conclusion: This study showed a higher proportion of females with AS and active disease using the BASDAI definition. When using the ASDAS-CRP definition these differences by gender were less pronounced. The impact of disease activity on HS appears to be higher in females than males.
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Rheumatic diseases are extensively managed with biological disease-modifying antirheumatic drugs (bDMARDs), but a notable proportion of patients withdraw in the long term because of lack of effectiveness, adverse events, or the patient's decision. The present real-world analysis showed the effectiveness, retention, and safety data collected in the Spanish BIOBADASER registry for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA, including ankylosing spondylitis (AS) and non-radiographic axSpA) treated with secukinumab, a human antibody against interleukin-17A (IL-17A), for more than 12 months. Six hundred and thirty-nine patients were analysed (350, 262, and 27 PsA, AS, and nr-axSpA patients, respectively). The results showed an improvement in the disease activity after 1 year of treatment, in terms of decreases of the mean Disease Activity Score 28 using C-reactive protein (DAS28-CRP), the mean Disease Activity Psoriatic Arthritis (DAPSA) score, swollen joint counts (SJC), and tender joint counts (TJC) in PsA patients and decreases in the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the mean Ankylosing Spondylitis Disease Activity Score (ASDAS) in axSpA patients. This improvement was maintained or increased after 2 and 3 years of treatment, indicating that secukinumab is effective in both naïve and non-responder patients. Retention rates were higher when secukinumab was used as the first-line biological treatment, although they were also adequate in the second and third lines of treatment. Collected safety data were consistent with previous reports.
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The better understanding of the safety of biologic DMARDs (bDMARDs), as well as the emergence of new bDMARDs against different therapeutic targets and biosimilars have likely influenced the use patterns of these compounds over time. The aim of this study is to assess changes in demographic characteristics, disease activity and treatment patterns in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) who started a first- or second-line biologic between 2007 and mid-2020. Patients diagnosed with RA, PsA or AS included in the BIOBADASER registry from January 2007 to July 2020 were included. According to the start date of a first- or second-line biologic therapy, patients were stratified into four time periods: 2007-2009; 2010-2013; 2014-2017; 2018-2020 and analyzed cross-sectionally in each period. Demographic and clinical variables, as well as the type of biologic used, were assessed. Generalized linear models were applied to study the evolution of the variables of interest over time periods, the diagnosis, and the interactions between them. A total of 4543 patients initiated a first biologic during the entire time frame of the study. Over the four time periods, disease evolution at the time of biologic initiation (p < 0.001), disease activity (p < 0.001), retention rate (p < 0.001) and the use of tumor necrosis factor inhibitors as a first-line treatment (p < 0.001) showed a significant tendency to decrease. Conversely, comorbidities, as assessed by the Charlson index (p < 0.001), and the percentage of patients using bDMARDs in monotherapy (p < 0.001), and corticosteroids (p < 0.001) tended to increase over time. Over the entire period of the study's analysis, 3289 patients started a second biologic. The following trends were observed: decreased DAS28 at switching (p < 0.001), lower retention rates (p = 0.004), and incremental changes to the therapeutic target between the first and second biologic (p < 0.001). From 2007 until now rheumatic patients who started a biologic were older, exhibited less clinical activity, presented more comorbidities, and switched to a different biologic more frequently and earlier.
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Artritis Psoriásica/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Biosimilares Farmacéuticos/uso terapéutico , Espondilitis Anquilosante/tratamiento farmacológico , Antirreumáticos/uso terapéutico , Artritis Psoriásica/epidemiología , Artritis Psoriásica/patología , Artritis Reumatoide/epidemiología , Artritis Reumatoide/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/epidemiología , Enfermedades Reumáticas/patología , España/epidemiología , Espondilitis Anquilosante/epidemiología , Espondilitis Anquilosante/patología , Inhibidores del Factor de Necrosis Tumoral/uso terapéuticoRESUMEN
OBJECTIVE: To assess the relationship between the increase of fecal calprotectin, anti-Saccharomyces cerevisiae antibodies (ASCA) and disease markers in a group of patients with spondyloarthritis. METHODS: We evaluated patients who were at least 18-years-old and met the Assessment in Spondyloarthritis International Society (ASAS) criteria for spondyloarthritis or the New York modified criteria. We analyzed activity criteria, physical function, analytical criteria (human leukocyte antigen [HLA] B27, fecal calprotectin, presence of ASCA, among others) and demographic data. RESULTS: We included 33 patients. All but one patient had normal ASCA values. We found statistical significance in the correlation of calprotectin with C-reactive protein (CRP) but not with other parameters. We also found a relationship between calprotectin levels and nonsteroidal anti-inflammatory drug (NSAID) intake (P=.001). We found no relationship between CRP levels and NSAID use. After discontinuation of NSAIDs for one month, we found no significant differences in calprotectin levels (P=.9). CONCLUSION: Fecal calprotectin is elevated in patients with spondyloarthritis and correlates positively with CRP. Level of fecal calprotectin is not altered by NSAID use. The amount of ASCA present does not change and does not correlate with any clinical parameters in the study population.
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Anticuerpos Antifúngicos/sangre , Heces/química , Complejo de Antígeno L1 de Leucocito/análisis , Saccharomyces cerevisiae/inmunología , Espondiloartritis/diagnóstico , Espondiloartritis/metabolismo , Adulto , Biomarcadores/análisis , Proteína C-Reactiva/análisis , Humanos , Persona de Mediana Edad , Espondiloartritis/sangreRESUMEN
Research in rheumatoid arthritis (RA) is increasingly focused on the discovery of biomarkers that could enable personalized treatments. The genetic biomarkers associated with the response to TNF inhibitors (TNFi) are among the most studied. They include 12 SNPs exhibiting promising results in the three largest genome-wide association studies (GWAS). However, they still require further validation. With this aim, we assessed their association with response to TNFi in a replication study, and a meta-analysis summarizing all non-redundant data. The replication involved 755 patients with RA that were treated for the first time with a biologic drug, which was either infliximab (n = 397), etanercept (n = 155) or adalimumab (n = 203). Their DNA samples were successfully genotyped with a single-base extension multiplex method. Lamentably, none of the 12 SNPs was associated with response to the TNFi in the replication study (p > 0.05). However, a drug-stratified exploratory analysis revealed a significant association of the NUBPL rs2378945 SNP with a poor response to etanercept (B = -0.50, 95% CI = -0.82, -0.17, p = 0.003). In addition, the meta-analysis reinforced the previous association of three SNPs: rs2378945, rs12142623, and rs4651370. In contrast, five of the remaining SNPs were less associated than before, and the other four SNPs were no longer associated with the response to treatment. In summary, our results highlight the complexity of the pharmacogenetics of TNFi in RA showing that it could involve a drug-specific component and clarifying the status of the 12 GWAS-drawn SNPs.
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Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Etanercept/uso terapéutico , Polimorfismo de Nucleótido Simple , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Antirreumáticos/uso terapéutico , Femenino , Marcadores Genéticos , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Farmacogenómica , Variantes Farmacogenómicas , Adulto JovenRESUMEN
AIMS: To describe the methodology of REAPSER (Spanish Registry of Recent-onset Psoriatic Arthritis), its strengths and limitations. The aim of this study is to identify prognostic factors for the clinical and radiographic course in a cohort of patients with psoriatic arthritis (PsA) diagnosed within 2years of symptom evolution. METHODS: Multicenter, observational and prospective study (with 2-year follow-up including annual visits). Baseline visit intended to reflect patient situation before the disease course was modified by treatments prescribed in rheumatology departments. Patients were invited to participate consecutively in one of their routine visits to the rheumatologist. 211 patients were included. Following data were collected: sociodemographic variables; employment situation; family history; personal history and comorbidities; anthropometric data; lifestyle; use of healthcare services; clinical situation at the time of PsA diagnosis; joint involvement and spinal pain; pain and overall assessment; enthesitis, dactylitis and uveitis; skin and nail involvement; functional situation and quality of life; radiographic evaluation; analytical determinations; treatment; axial and peripheral flare-ups. CONCLUSIONS: The REAPSER study includes a cohort of patients with recent-onset PsA, before the disease course was modified by disease-modifying antirheumatic drugs prescribed in rheumatology departments. Exhaustive information collected in each visit is expected to be an important data source for future analysis.
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Artritis Psoriásica/diagnóstico por imagen , Progresión de la Enfermedad , Sistema de Registros , Adulto , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Anamnesis , Selección de Paciente , Pronóstico , Estudios Prospectivos , Radiografía , España , Factores de TiempoRESUMEN
Genetic biomarkers are sought to personalize treatment of patients with rheumatoid arthritis (RA), given their variable response to TNF inhibitors (TNFi). However, no genetic biomaker is yet sufficiently validated. Here, we report a validation study of 18 previously reported genetic biomarkers, including 11 from GWAS of response to TNFi. The validation was attempted in 581 patients with RA that had not been treated with biologic antirheumatic drugs previously. Their response to TNFi was evaluated at 3, 6 and 12 months in two ways: change in the DAS28 measure of disease activity, and according to the EULAR criteria for response to antirheumatic drugs. Association of these parameters with the genotypes, obtained by PCR amplification followed by single-base extension, was tested with regression analysis. These analyses were adjusted for baseline DAS28, sex, and the specific TNFi. However, none of the proposed biomarkers was validated, as none showed association with response to TNFi in our study, even at the time of assessment and with the outcome that showed the most significant result in previous studies. These negative results are notable because this was the first independent validation study for 12 of the biomarkers, and because they indicate that prudence is needed in the interpretation of the proposed biomarkers of response to TNFi even when they are supported by very low p values. The results also emphasize the requirement of independent replication for validation, and the need to search protocols that could increase reproducibility of the biomarkers of response to TNFi.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Marcadores Genéticos/genética , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
INTRODUCTION: We have hypothesized that incompatibility between the G1m genotype of the patient and the G1m1 and G1m17 allotypes carried by infliximab (INX) and adalimumab (ADM) could decrease the efficacy of these anti-tumor necrosis factor (anti-TNF) antibodies in the treatment of rheumatoid arthritis (RA). METHODS: The G1m genotypes were analyzed in three collections of patients with RA totaling 1037 subjects. The first, used for discovery, comprised 215 Spanish patients. The second and third were successively used for replication. They included 429 British and Greek patients and 393 Spanish and British patients, respectively. Two outcomes were considered: change in the Disease Activity Score in 28 joint (ΔDAS28) and the European League Against Rheumatism (EULAR) response criteria. RESULTS: An association between less response to INX and incompatibility of the G1m1,17 allotype was found in the discovery collection at 6 months of treatment (P = 0.03). This association was confirmed in the replications (P = 0.02 and 0.08, respectively) leading to a global association (P = 0.001) that involved a mean difference in ΔDAS28 of 0.4 units between compatible and incompatible patients (2.3 ± 1.5 in compatible patients vs. 1.9 ± 1.5 in incompatible patients) and an increase in responders and decrease in non-responders according to the EULAR criteria (P = 0.03). A similar association was suggested for patients treated with ADM in the discovery collection, but it was not supported by replication. CONCLUSIONS: Our results suggest that G1m1,17 allotypes are associated with response to INX and could aid improved therapeutic targeting in RA.
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Adalimumab/genética , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Inmunoglobulina G/genética , Infliximab/genética , Adalimumab/uso terapéutico , Adulto , Antirreumáticos/uso terapéutico , Artritis Reumatoide/inmunología , Secuencia de Bases , Femenino , Genotipo , Humanos , Alotipos de Inmunoglobulinas , Infliximab/uso terapéutico , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Polimorfismo de Nucleótido Simple , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
El daño radiográfico habitualmente se produce de manera lenta en los pacientes con espondiloartritis, pero conlleva una importante disminución de la capacidad funcional y un deterioro de la calidad de vida. En la actualidad se sabe que diversos tratamientos, entre los cuales se encuentran las terapias biológicas y los antiinflamatorios no esteroideos, producen una mejoría clínica evidente, pero los datos en cuanto al efecto sobre el daño estructural no están tan claros. Por tanto, parece importante la valoración de la modificación de esta variable (daño radiográfico) por las distintas terapias que manejamos en nuestros pacientes con espondiloartritis tanto a nivel axial como periférico
Radiographic damage usually occurs slowly in patients with spondyloarthritis but substantially reduces functional capacity and impairs quality of life. It is currently known that various treatments, including biological therapies and NSAIDs, produce evident clinical improvement but data on their effect on structural damage is less clear. Therefore, it seems important to assess modification of this variable (radiographic damage) by the various therapies used in patients with spondyloarthritis, whether axial or peripheral
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Humanos , Espondiloartritis/tratamiento farmacológico , Remodelación Ósea/fisiología , Sacroileítis/tratamiento farmacológico , Terapia Biológica/métodos , Antiinflamatorios no Esteroideos/uso terapéutico , Espondiloartritis/complicaciones , Ustekinumab/farmacocinética , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
OBJETIVO: Valorar la relación entre la calprotectina fecal, ASCA y marcadores de enfermedad en espondiloartritis (Spa). MÉTODOS: Se evaluaron pacientes ≥18años que cumplían criterios ASAS o criterios modificados de Nueva York. Se analizan criterios de actividad, función física, analíticos y datos demográficos. RESULTADOS: Se incluyeron 33 pacientes. Todos excepto uno tenían valores normales de ASCA. Encontramos correlación significativa entre calprotectina y PCR pero no con otros parámetros, ni entre los niveles de calprotectina y la toma de AINE (p = 0,001). Tampoco entre los niveles de PCR y el uso de AINE. Después de retirar los AINE no encontramos diferencias en los niveles de calprotectina (p = 0,9). CONCLUSIÓN: La calprotectina fecal está elevada en pacientes con Spa y se correlaciona positivamente con la PCR. La elevación de la calprotectina fecal no se ve alterada por el uso de AINE. La cantidad de ASCA no cambia y no se correlaciona con ningún parámetro clínico en el estudio poblacional
OBJECTIVE: To assess the relationship between the increase of fecal calprotectin, anti-Saccharomyces cerevisiae antibodies (ASCA) and disease markers in a group of patients with spondyloarthritis. METHODS: We evaluated patients who were at least 18-years-old and met the Assessment in Spondyloarthritis International Society (ASAS) criteria for spondyloarthritis or the New York modified criteria. We analyzed activity criteria, physical function, analytical criteria (human leukocyte antigen [HLA] B27, fecal calprotectin, presence of ASCA, among others) and demographic data. RESULTS: We included 33 patients. All but one patient had normal ASCA values. We found statistical significance in the correlation of calprotectin with C-reactive protein (CRP) but not with other parameters. We also found a relationship between calprotectin levels and nonsteroidal anti-inflammatory drug (NSAID) intake (P=.001). We found no relationship between CRP levels and NSAID use. After discontinuation of NSAIDs for one month, we found no significant differences in calprotectin levels (P=.9). CONCLUSION: Fecal calprotectin is elevated in patients with spondyloarthritis and correlates positively with CRP. Level of fecal calprotectin is not altered by NSAID use. The amount of ASCA present does not change and does not correlate with any clinical parameters in the study population
Asunto(s)
Humanos , Adulto , Persona de Mediana Edad , Anticuerpos Antifúngicos/sangre , Heces/química , Complejo de Antígeno L1 de Leucocito/análisis , Saccharomyces cerevisiae/inmunología , Espondiloartritis/diagnóstico , Espondiloartritis/metabolismo , Biomarcadores/análisis , Proteína C-Reactiva/análisis , Espondiloartritis/sangreRESUMEN
INTRODUCTION: In this study, our aim was to elucidate the role of four polymorphisms identified in a prior large genome-wide association study (GWAS) in which the investigators analyzed the responses of patients with rheumatoid arthritis (RA) to treatment with tumor necrosis factor inhibitors (TNFi). The authors of that study reported that the four genetic variants were significantly associated. However, none of the associations reached GWAS significance, and two subsequent studies failed to replicate these associations. METHODS: The four polymorphisms (rs12081765, rs1532269, rs17301249 and rs7305646) were genotyped in a total of 634 TNFi-treated RA patients of Spanish Caucasian origin. Four outcomes were evaluated: changes in the Disease Activity Score in 28 joints (DAS28) after 6 and 12 months of treatment and classification according to the European League Against Rheumatism (EULAR) response criteria at the same time points. Association with DAS28 changes was assessed by linear regression using an additive genetic model. Contingency tables of genotype and allele frequencies between EULAR responder and nonresponder patients were compared. In addition, we combined our data with those of previously reported studies in a meta-analysis including 2,998 RA patients. RESULTS: None of the four genetic variants showed an association with response to TNFi in any of the four outcomes analyzed in our Spanish patients. In addition, only rs1532269 yielded a suggestive association (P = 0.0033) with the response to TNFi when available data from previous studies were combined in the meta-analysis. CONCLUSION: Our data suggest that the rs12081765, rs1532269, rs17301249 and rs7305646 genetic variants do not have a role as genetic predictors of TNFi treatment outcomes.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Polimorfismo de Nucleótido Simple , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Anciano , Femenino , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJETIVOS: Describir la metodología del Registro Español de Artritis Psoriásica de reciente comienzo de la Sociedad Española de Reumatología (REAPSER), así como sus fortalezas y limitaciones. El objetivo principal del proyecto es identificar factores pronósticos de la evolución clínica y radiográfica en una cohorte de pacientes que padecen artritis psoriásica (APs) diagnosticada con menos de 2 años de evolución. MATERIAL Y MÉTODO: Estudio observacional, prospectivo (2 años de seguimiento; periodicidad anual de las visitas), multicéntrico. La intención en la visita basal fue reflejar la situación del paciente antes de que la evolución de la enfermedad se viese modificada por los tratamientos pautados en los servicios de reumatología. Los pacientes fueron invitados a participar consecutivamente en una de sus visitas habituales al reumatólogo. El tamaño muestral finalmente alcanzado fue de 211 pacientes. Se recogen datos sociodemográficos; de situación laboral; historia familiar; antecedentes personales y comorbilidad; antropométricos; estilo de vida; uso de los servicios de salud; situación clínica al diagnóstico de APs; afectación articular y dolor espinal; dolor y valoración global de la enfermedad; entesitis, dactilitis y uveítis; afectación cutánea y ungueal; situación funcional y calidad de vida; evaluación radiográfica; determinaciones analíticas; tratamiento; brotes en esqueleto axial y periférico. CONCLUSIONES: El estudio REAPSER incluye una cohorte de pacientes con APs de inicio reciente reclutados antes de que la evolución de la enfermedad se viese modificada por la prescripción de FAME en los servicios de reumatología. Se espera que la información exhaustiva recogida en las visitas suponga una amplia fuente de datos para futuros análisis
AIMS: To describe the methodology of REAPSER (Spanish Registry of Recent-onset Psoriatic Arthritis), its strengths and limitations. The aim of this study is to identify prognostic factors for the clinical and radiographic course in a cohort of patients with psoriatic arthritis (PsA) diagnosed within 2 years of symptom evolution. METHODS: Multicenter, observational and prospective study (with 2-year follow-up including annual visits). Baseline visit intended to reflect patient situation before the disease course was modified by treatments prescribed in rheumatology departments. Patients were invited to participate consecutively in one of their routine visits to the rheumatologist. 211 patients were included. Following data were collected: sociodemographic variables; employment situation; family history; personal history and comorbidities; anthropometric data; lifestyle; use of healthcare services; clinical situation at the time of PsA diagnosis; joint involvement and spinal pain; pain and overall assessment; enthesitis, dactylitis and uveitis; skin and nail involvement; functional situation and quality of life; radiographic evaluation; analytical determinations; treatment; axial and peripheral flare-ups. CONCLUSIONS: The REAPSER study includes a cohort of patients with recent-onset PsA, before the disease course was modified by disease-modifying antirheumatic drugs prescribed in rheumatology departments. Exhaustive information collected in each visit is expected to be an important data source for future analysis