Treatment with methotrexate and risk of relapses in patients with giant cell arteritis in clinical practice.

OBJECTIVES: To assess the incidence and the risk of relapses in giant cell arteritis (GCA) patients treated with and without methotrexate (MTX) in clinical practice. Other associated factors were also investigated. METHODS: An inception cohort of GCA was assembled in the out-patient clinic at Hospital Clínico San Carlos, including patients from the date of diagnosis (Jan-1991 until Sept-2013), and followed-up until lost of follow up or Sept-2014. MAIN OUTCOME: relapse defined as recurrence of symptoms or signs of GCA with high ESR and the need to increase glucocorticoids at least 10mg over the previous dose. The independent variable was exposure to MTX over time. Covariables: Sociodemographic, clinical, and treatment. Incidence rates of relapses (IR) per 100 patient-year with their 95% confidence intervals [CI] were estimated using survival techniques. MTX influence on relapses was analysed by Cox models. RESULTS: 168 patients were included (675 patient-year). 31% of patients had relapses (IR of 12 [9.6-14.9]), and the median number of relapses was 1[1-2]. 65% of the patients were on MTX, (mean dose: 10mg). In the bivariate analysis, the risk of relapses in patients with and without MTX did not achieve statistical signification (p=0.1). After adjusting in the multivariate analysis, exposure to MTX had 72% less risk of relapse compared to those without MTX (p<0.05). Other variables included in the final model were: visual alterations and malaise at clinical presentation of GCA. CONCLUSIONS: The use of MTX seems to decrease the risk of recurrences. We also found other factors influencing on relapses.

Difficult-to-treat rheumatoid arthritis (D2T RA): clinical issues at early stages of disease.

OBJECTIVES: Most studies on difficult-to-treat rheumatoid arthritis (D2T RA) have focused on established RA. Here, we analyse whether disease activity in the early stages of RA could influence progression to a D2T RA under real-life conditions. Other clinical and treatment-related factors were also analysed. METHODS: A longitudinal multicentre study of patients with RA was conducted from 2009 to 2018. Patients were followed up until January 2021. D2T RA was defined based on EULAR criteria (treatment failure, signs suggestive of currently active/progressive disease and management being perceived as problematic by the rheumatologist and/or patient). The main variable was disease activity in the early stages. The covariates were sociodemographic, clinical and treatment-related factors. We ran a multivariable logistic regression analysis to investigate risk factors associated with progression to D2T RA. RESULTS: The study population comprised 631 patients and 35 (5.87%) developed D2T RA. At the time of diagnosis, the D2T RA group were younger, with a higher disability, 28-joint Disease Activity Score (DAS28) score, tender joint count and pain scores. In our final model, DAS28 was not statistically significantly associated with D2T RA. No differences were found between groups for therapy. Disability was independently associated with D2T RA (OR: 1.89; p=0.01). CONCLUSIONS: In this cohort of patients newly diagnosed with RA, our results do not allow us to prove the influence of active disease according to DAS28. However, we did find that younger patients and those with elevated initial disability scores are more likely to develop D2T RA regardless of other factors.

Role of diagnostic imaging in psoriatic arthritis: how, when, and why.

Psoriasis is a common skin disease. Up to 30% of patients with psoriasis develop psoriatic arthritis (PsA) resulting, by far, the most prevalent coexisting condition. Heterogeneity of clinical and radiological presentation is a major challenge to diagnosis of PsA. Initial reports about PsA emphasized a benign course in most patients, but it is now recognized that psoriatic arthritis often leads to impaired function and a reduced quality of life. PsA is a progressive disease characterized by diverse clinical features, often resulting in diagnostic delay and treatment that are associated with poor clinical and structural outcomes. New effective treatments may halt PsA progression, and consequently, treatment goals have evolved from simple reduction of pain to achieving full remission or minimal disease activity. This emerging treat-to-target strategy paradigm emphasize a need for early diagnosis; sensitive imaging techniques may be of value in this process. While radiography and CT depict structural damage, US and MRI have emerged as helpful tools to evaluate magnitude and severity of active inflammatory lesions. This review aims to describe the role of imaging modalities in diagnosis, follow-up and prognosis of PsA.

Immunosuppressive Drug Discontinuation in Noninfectious Uveitis From Real-Life Clinical Practice: A Survival Analysis.

PURPOSE: To assess in uveitis patients the rate of immunosuppressive drug (ISD) discontinuation in real-life clinical practice, comparing this rate among ISDs. DESIGN: Longitudinal retrospective cohort study. METHODS: We included uveitis patients attending a tertiary eye referral center from Madrid (Spain) between 1989 and 2015, prescribed any ISDs (cyclosporine, methotrexate, azathioprine, anti-TNF drugs, or others). Our main outcome was discontinuation of all ISDs owing to clinical efficacy, inefficacy, adverse drug reaction (ADR), and other medical causes. Discontinuation rates (DRs) per 100 patient-years were estimated. Variables associated with specific-cause discontinuations were analyzed using Cox bivariate and multivariate models. RESULTS: We analyzed 110 patients with 263 treatment courses and 665.2 patient-years of observation. Cyclosporine (66.4%), methotrexate (47.3%), azathioprine (30.9%), and anti-TNFs (30.9%) were the most frequently used ISDs. Treatment was suspended in 136 cases (mostly owing to clinical efficacy [38.2%], inefficacy [26.5%], and ADRs [22.8%]). All-cause DR with 95% confidence interval was 20.4 [17.3-24.2]. Retention rates at 1 and 10 years were 74% and 16%, respectively. In the multivariate analysis, combined treatment exhibited higher DRs owing to clinical efficacy than other ISDs in monotherapy. Conversely, nonbiologic combination therapy with azathioprine exhibited the highest DR owing to ADRs. CONCLUSIONS: Clinical efficacy was the most frequent cause for ISD discontinuation, followed by inefficacy and ADRs. DR owing to efficacy was higher for combination therapy. Furthermore, nonbiologic combination therapy with azathioprine was associated with a higher DR owing to ADRs.

Safety of disease-modifying antirheumatic drugs and biologic agents for rheumatoid arthritis patients in real-life conditions.

OBJECTIVE: The aim of this study was to describe the incidence rate (IR) of adverse drug reactions (ADRs) in daily clinical practice, related to disease-modifying antirheumatic drugs (DMARDs) and biologic agents (BA) in rheumatoid arthritis (RA) patients, and to analyze factors causing discontinuation due to ADRs. METHODS: This was a prospective observational study (October 2010 to October 2011). RA patients who were attended in our hospital taking DMARDs or BA during the study period were included. ADRs were injuries related to these drugs and registered with a software system in routine visits. ADRs could be mild (lowering dosage), moderate (drug discontinuation), or severe (hospital admission). The IR of ADR per 100 patient-years was estimated using survival techniques. Cox regression models (HR; 95% confidence interval) were used to explore factors associated with discontinuation due to ADRs. RESULTS: In total, 1202 patients were analyzed, with 158 ADRs (IR = 15.2). Of all ADRs, 80.4% required drug discontinuation (IR = 12.2). Age, less disease and therapy duration, taking corticoids, and combined therapy versus monotherapy (HR = 3; 95% CI: 2.0-4.4) were the factors independently associated to discontinuation due to ADRs. We did not find statistical differences between the different monotherapy regimens. Regarding combinations, Methotrexate + BA had the lowest risk of discontinuation compared to the rest (HR = 0.24; 95% CI: 0.09-0.6). CONCLUSIONS: We have estimated the incidence of ADRs related to DMARDs/BA in real-life conditions. We confirm the role of combined therapy in the development of discontinuations due to ADRs, except for BA + MTX, which did not show an increase of toxicity compared to monotherapy. This combination seems to be safer than others.

A meta-analysis of mortality in rheumatic diseases.

INTRODUCTION: Data reporting mortality in rheumatic diseases vary widely. The objective of this systematic review and meta-analysis of published data is to provide an accurate overview of the current risk of mortality in rheumatic diseases. METHODS: Systematic review and meta-analysis of published studies identified by a sensitive search using free text and MeSH synonyms of "mortality" and of "rheumatic diseases", in general and by specific diagnoses. Eligibility criteria were (1) study population with rheumatoid arthritis, systemic lupus erythemathosus, systemic sclerosis, vasculitis, osteoarthritis, osteoporosis, dermatomyositis, or spondyloarthritis; (2) outcome of interest mortality, reported as an standardized mortality ratio (SMR), or easily calculated from data reported; and (3) cohorts or longitudinal observational studies. Assessment of risk of bias relied on the New Castle-Ottawa scale for cohorts; only moderate to high quality studies were included. Separate meta-SMRs were calculated for specific diagnoses. Heterogeneity was studied with meta-regression. RESULTS: A total of 32 studies were included, none in spondyloarthritis or osteoarthritis. The overall pooled SMR was 2.03 (95% confidence interval (CI) 1.79-2.29), ranging from 1.36 in psoriatic arthritis to 4.80 in vasculitis. The largest individual overall SMR came from studies on inflammatory diseases, and the specific SMR were very high for infections and pulmonary events. Heterogeneity between studies was large; however, the analysis of such heterogeneity within diseases did not provide any association with the collected variables. CONCLUSIONS: Based on our results and on the good quality of the included studies, we can conclude that rheumatic diseases increase in general the risk of death, and especially inflammatory diseases.

A meta-analysis of mortality in rheumatic diseases

Introducción: Los datos de mortalidad en las enfermedades reumáticas es muy variable. El objetivo de esta revisión sistemática y meta-análisis de datos publicados es proporcionar una visión general más precisa del riesgo actual y mortalidad en las enfermedades reumáticas. Métodos: Revisión sistemática y meta-análisis de estudios publicados e identificados por una búsqueda utilizando texto libre y sinónimos MeSH de "mortalidad" y "enfermedades reumáticas", en general, y por diagnósticos específicos. Los criterios de selección fueron: 1) población de estudio con artritis reumatoide, lupus eritematoso sistémico, esclerosis sistémica, vasculitis, osteoartritis, osteoporosis, dermatomiositis, o espondiloartritis, 2) resultados de mortalidad de interés, reportados como SMR, o fácilmente calculados a partir de los datos comunicados, y 3) cohortes longitudinales o estudios observacionales. Evaluación del riesgo de sesgo basado en la escala de cohortes New Castle-Ottawa, sólo estudios de moderada a alta calidad fueron incluidos. Se calculó meta-SMR para diagnósticos específicos. La heterogeneidad se estudió con meta-regresión. Resultados: Un total de 32 estudios fueron incluidos, ninguno de espondiloartritis o osteoartritis. El SMR general combinada fue 2,03 (IC 95%: 1,79 a 2,29), desde 1,36 en la artritis psoriásica a 4,80 en las vasculitis. El mayor SMR general individual fue a partir de estudios sobre enfermedades inflamatorias, y SMR específicos fueron muy altos para las infecciones y reacciones pulmonares. La heterogeneidad entre los estudios era grande, sin embargo, el análisis de heterogeneidad dentro de las enfermedades no presentó ninguna asociación con las variables recogidas. Conclusiones: En base a los resultados y la buena calidad de los estudios incluidos, se puede concluir que las enfermedades reumáticas en general aumentan el riesgo de muerte, y especialmente las enfermedades inflamatorias (AU)

Introduction: Data reporting mortality in rheumatic diseases vary widely. The objective of this systematic review and meta-analysis of published data is to provide an accurate overview of the current risk of mortality in rheumatic diseases. Methods: Systematic review and meta-analysis of published studies identified by a sensitive search using free text and MeSH synonyms of "mortality" and of "rheumatic diseases", in general and by specific diagnoses. Eligibility criteria were (1) study population with rheumatoid arthritis, systemic lupus erythemathosus, systemic sclerosis, vasculitis, osteoarthritis, osteoporosis, dermatomyositis, or spondyloarthritis; (2) outcome of interest mortality, reported as an standardized mortality ratio (SMR), or easily calculated from data reported; and (3) cohorts or longitudinal observational studies. Assessment of risk of bias relied on the New Castle-Ottawa scale for cohorts; only moderate to high quality studies were included. Separate meta-SMRs were calculated for specific diagnoses. Heterogeneity was studied with meta-regression. Results: A total of 32 studies were included, none in spondyloarthritis or osteoarthritis. The overall pooled SMR was 2.03 (95% confidence interval (CI) 1.79-2.29), ranging from 1.36 in psoriatic arthritis to 4.80 in vasculitis. The largest individual overall SMR came from studies on inflammatory diseases, and the specific SMR were very high for infections and pulmonary events. Heterogeneity between studies was large; however, the analysis of such heterogeneity within diseases did not provide any association with the collected variables. Conclusions: Based on our results and on the good quality of the included studies, we can conclude that rheumatic diseases increase in general the risk of death, and especially inflammatory diseases (AU)