A potential point of concern among clinicians is whether results derived from the clinical trials can be reasonably applied or generalised to a definable group of patients seen in real world. It can ...be the case of the GiACTA study that is a phase III randomised controlled trial of tocilizumab (TCZ) in giant cell arteritis (GCA). To address this question, we compared the clinical features and the responses to TCZ from the GiACTA trial patients with those from a series of GCA seen in the daily clinical practice.
Comparative study of clinical features between patients from the GiACTA trial (overall n=251) and those from a multicentre series of real-world GCA patients undergoing TCZ therapy (n=134). The diagnosis of GCA in the GiACTA trial was established by the ACR modified criteria whereas in the series of real-world patients it was made by using the ACR criteria, a positive biopsy of temporal artery or the presence of imaging techniques consistent with large-vessel vasculitis in individuals who presented cranial symptoms of GCA. GiACTA trial patients received subcutaneous TCZ (162 mg every 1 or 2 weeks) whereas those from the clinical practice series were treated using standard IV dose (8 mg/kg/month) or subcutaneous (162 mg/week).
Real-life patients undergoing TCZ were older with longer disease duration and higher values of ESR and had received conventional immunosuppressive therapy (mainly methotrexate) more commonly than those included in the GiACTA trial. Despite clinical differences, TCZ was equally effective in both GiACTA trial and clinical practice patients. However, serious infections were more commonly observed in GCA patients recruited from the clinical practice.
Despite clinical differences with patients recruited in clinical trials, data from real-life patients confirm the efficacy of TCZ in GCA.
Digestive involvement (DI) has been reported in 10-30% of primary Sjögren's syndrome (pSS) patients, and few studies have systematically analysed the prevalence of DI in pSS patients. The aim of this ...study was to describe DI prevalence in pSS patients from the Sjögrenser Study, and to analyse its clinical associations.
All patients included in the Sjögrenser study, a Spanish multicentre randomised cohort, containing demographic, clinical and histologic data, have been analysed retrospectively. Patients were classified according to the presence of DI (oesophageal, gastric, intestinal, hepatic and pancreatic), and we have performed DI clinical associations, descriptive statistics, Student t or χ2 test, and uni and multivariate logistic regression.
From 437 included patients, 95% were women, with a median age of 58 years, 71 (16.2%) presented DI: 21 (29.5%) chronic atrophic gastritis, 12 (16.9%) oesophageal motility dysfunction, 3 (4.2%) lymphocytic colitis, 18 (25.3%) primary biliary cholangitis, 15 (21.1%) autoimmune hepatitis, 7 (9.8%) pancreatic involvement and 5 (7%) coeliac disease. Half of them developed DI at the same time or after pSS diagnosis. Patients with DI were significantly older at pSS diagnosis (p=0.032), more frequently women (p=0.009), presented more autoimmune hypothyroidism and C3 hypocomplementaemia (p=0.040), and were treated more frequently with glucocorticoids, immunosuppressant and biologic therapies. Patients with pancreatic involvement presented more central nervous system and renal involvement, Raynaud's phenomenon, lymphoma and C3/C4 hypocomplementaemia.
DI is frequent in Sjögrenser patients, mainly in the form of autoimmune disorders, and seem to be associated with a more severe phenotype. Our results suggest that DI should be evaluated in pSS patients, especially those with more severe disease.
OBJECTIVETo describe the frequency of polyautoimmunity and multiple autoimmune syndrome in patients with rheumatoid arthritis (RA) and patients with systemic lupus erythematosus (SLE).
PATIENTS AND ...METHODSThis was a cross-sectional observational study of patients with RA, SLE, and controls without autoimmune rheumatic disease. Cases were those with RA according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria and SLE according to the 2019 American College of Rheumatology/European League Against Rheumatism criteria, consecutively recruited in a rheumatology clinic. Controls were subjects with no rheumatic autoimmune disease (AIDs) recruited in the same area. Patients filled out a questionnaire on polyautoimmunity. Variables of interest were polyautoimmunity (RA or SLE with other AIDs), whereas secondary variables were rheumatic, skin, endocrine, digestive, and neurological AIDs. Multiple autoimmune syndrome is defined as the presence of 3 or more AIDs and a family history of AIDs. Statistical analyses performed were descriptive, bivariate, and multivariate (dependent variablepolyautoimmunity).
RESULTSThe study population comprised 109 patients with RA, 105 patients with SLE, and 88 controls. Polyautoimmunity was recorded in 15 patients with RA (13.8%), 43 with SLE (41%), and 2 controls (2.2%). The most frequent AID in RA was Sjögren syndrome (53.3%), followed by Hashimoto thyroiditis and psoriasis; the most frequent AIDs in SLE were Sjögren syndrome (55.8%) and antiphospholipid syndrome (30.2%), followed by Hashimoto thyroiditis. Obesity was associated with polyautoimmunity in RA (odds ratio OR, 3.362; p = 0.034). In SLE, joint damage (OR, 2.282; p = 0.038) and anti-RNP antibodies (OR, 5.095; p = 0.028) were risk factors for polyautoimmunity, and hydroxychloroquine was a protective factor (OR, 0.190; p = 0.004).
CONCLUSIONSPolyautoimmunity is frequent in RA and even more frequent in SLE. It was associated with obesity in RA and with joint damage and anti-RNP in SLE. Hydroxychloroquine was a protector.
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.
The aims of this study were to evaluate adherence of rheumatoid arthritis (RA) patients to biological disease-modifying antirheumatic drugs (bDMARDs), identify potential risk factors, and analyze the ...discriminative ability of the Morisky–Green test (MGT) to detect bDMARD nonadherence. One hundred and seventy-eight adult RA patients treated with bDMARDs were included. Adherence was measured using the medication possession ratio (MPR) of the previous 6 months. An MPR >80% was considered good adherence. Patient demographics, clinical characteristics, and MGT scores were assessed through a standardized clinical interview at the cross-sectional date. One-hundred and twelve patients (63%) were taking subcutaneous bDMARDs, while 66 (37%) were taking intravenous drugs. One-hundred fifty-eight (88.8%) showed good adherence to bDMARDs, while 79 (61.2%) also correctly took concomitant conventional synthetic DMARDs (csDMARDs). In logistic regression models, nonadherence to bDMARDs was associated with higher disease activity odds ratio (OR) 1.45; 95% CI, 1.03–2.03;
p
= 0.032 and subcutaneous route (OR 3.70; 95% CI 1.02–13.48;
p
= 0.040). MGT accurately identified an MPR >80% of bDMARDs in 76.9% of the patients. A sensitivity of 78%, specificity of 70%, positive predictive value of 95.3%, negative predictive value of 28.5%, positive likelihood ratio (LR) of 2.6, and negative LR of 0.3% were obtained. Adherence may be good for bDMARDs but is low for csDMARDs. Low adherence for bDMARDs is associated with poorer disease control during the past 6 months and use of subcutaneous route. These findings should alert doctors to consider possible low adherence before declaring treatment failure.
ObjectivesTo describe the prevalence of insulin resistance (IR) in patients with established rheumatoid arthritis (RA) and to analyse the contribution of cumulative inflammatory burden and other ...factors to its development.DesignObservational cross-sectional study.ParticipantsPatients with RA and controls matched for age, sex and Body Mass Index. We excluded patients with diabetes.SettingsPatients from an RA inception cohort at Hospital Regional Universitario de Málaga, Spain, were recruited between September 2016 and May 2018.Primary and secondary outcome measuresIR was evaluated using the homeostasis model assessment for IR and beta-cell function and the quantitative insulin sensitivity check index. Other variables included the cumulative 28-Joint Disease Activity Score (DAS28) with C reactive protein (CRP) body composition and cytokines. Two logistic regression models were constructed to identify factors associated with IR in patients with RA.ResultsEighty-nine patients with RA and 80 controls were included. The prevalence of IR was similar in both cases and controls. Inflammatory activity was controlled appropriately in patients during follow-up (mean DAS28 3.1 (0.8)). The presence of IR in patients with RA was associated with obesity (OR 6.01, 95% CI 1.9 to 8.7), higher cumulative DAS28-CRP values during follow-up (OR 2.8, 95% CI 1.3 to 6.0), and higher interleukin-1β levels (OR 1.6, 95% CI 1.1 to 2.4). The second model showed that the risk of IR increased by 10% for each kilogram of excess body fat.ConclusionIn patients with well-controlled, established RA, IR is associated mainly with poorer control of inflammation from diagnosis and with obesity, specifically total fat mass.
Sarcopenia is a major cause of morbidity in rheumatoid arthritis patients. Our purpose was to determine whether polyautoimmunity is associated with sarcopenia and alterations in whole body ...composition in patients with rheumatoid arthritis (RA).
We performed a cross-sectional observational study of a series of cases of RA. All patients were recruited consecutively from a rheumatology clinic. Body composition by dual-energy x-ray absorptiometry (DEXA) was assessed. The variables of interest were polyautoimmunity (RA associated with other autoimmune diseases), sarcopenia, fat mass, and body mass index (BMI). Other variables included were clinical-analytical and inflammatory cytokines and adipokines. The relationship between sarcopenic obesity and the presence of polyautoimmunity was studied using multivariate analysis.
Of the 94 patients with RA included in the study, 15 (16%) had polyautoimmunity. A total of 23 patients with RA (24.5%) had sarcopenia, which was more prevalent in patients with polyautoimmunity than in patients without polyautoimmunity (46.7% vs 20.3%; p = .029). Sarcopenia was not associated with body fat content (p = .870) or with BMI (p = .998). The multivariate analysis showed the factors associated with polyautoimmunity in RA to be sarcopenia (odds ratio 95% CI, 4.80 1.49-13.95), BMI (1.18 1.04-1.35), and resistin (1.249 1.01-1.53).
Sarcopenia and obesity were more prevalent in patients with RA and polyautoimmunity. Resistin values were also higher in this group than in patients with RA without polyautoimmunity.
Analizar si la poliautoinmunidad en los pacientes con artritis reumatoide (AR) se asocia con sarcopenia y alteraciones de la composición corporal total.
Estudio observacional transversal de una serie de casos de pacientes con AR, reclutados consecutivamente de la consulta de reumatología. Se evaluó la composición corporal mediante absorciometria de rayos X de energia dual (DXA). Las variables de interés fueron la poliautoinmunidad (AR asociada a otras enfermedades autoinmunes), sarcopenia, masa grasa e índice de masa corporal. Otras variables incluidas fueron clínico-analíticas y citoquinas inflamatorias y adipoquinas. La relación entre obesidad sarcopénica y la presencia de poliautoinmunidad se estudió mediante análisis multivariable.
De los 94 pacientes con AR incluidos en el estudio, 15 (16%) tenían poliautoinmunidad. Un total de 23 (24,5%) pacientes con AR presentaron sarcopenia, la cual fue más prevalente en los pacientes con poliautoinmunidad en comparación con los demás (46,7 vs. 20,3%; p = 0,029). La sarcopenia no se asoció con el contenido corporal de grasa en la composición corporal (p = 0,870) ni con el índice de masa corporal (IMC) (p = 0,998). En el análisis multivariante, los factores asociados a la poliautoinmunidad en AR fueron la sarcopenia (odds ratio IC 95%, 4,80 1,49-13,95), el IMC (1,18 1,04-1,35), y la resistina (1,249 1,01-1,53).
Los pacientes con AR con poliautoinmunidad mostraron una mayor prevalencia de sarcopenia y obesidad, además tuvieron valores más elevados de resistina en comparación con pacientes con AR sin poliautoinmunidad.
To determine the incidence and risk factors of first cardiovascular event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD).
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.
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).
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.
Objective
To compare the prevalence of the main comorbidities in 2 large cohorts of patients with primary Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE), with a focus on ...cardiovascular (CV) diseases.
Methods
This was a cross‐sectional multicenter study where the prevalence of more relevant comorbidities in 2 cohorts was compared. Patients under followup from SJOGRENSER (Spanish Rheumatology Society Registry of Primary SS) and RELESSER (Spanish Rheumatology Society Registry of SLE), and who fulfilled the 2002 American–European Consensus Group and 1997 American College of Rheumatology classification criteria, respectively, were included. A binomial logistic regression analysis was carried out to explore potential differences, making general adjustments for age, sex, and disease duration and specific adjustments for each variable, including CV risk factors and treatments, when appropriate.
Results
A total of 437 primary SS patients (95% female) and 2,926 SLE patients (89% female) were included. The mean age was 58.6 years (interquartile range IQR 50.0–69.9 years) for primary SS patients and 45.1 years (IQR 36.4–56.3 years) for SLE patients (P < 0.001), and disease duration was 10.4 years (IQR 6.0–16.7 years) and 13.0 years (IQR 7.45–19.76 years), respectively (P < 0.001). Smoking, dyslipidemia, and arterial hypertension were associated less frequently with primary SS (odds ratio OR 0.36 95% confidence interval (95% CI) 0.28–0.48, 0.74 95% CI 0.58–0.94, and 0.50 95% CI 0.38–0.66, respectively) as were life‐threatening CV events (i.e., stroke or myocardial infarction; OR 0.57 95% CI 0.35–0.92). Conversely, lymphoma was associated more frequently with primary SS (OR 4.41 95% CI 1.35–14.43). The prevalence of severe infection was lower in primary SS than in SLE (10.1% versus 16.9%; OR 0.54 95% CI 0.39–0.76; P < 0.001).
Conclusion
Primary SS patients have a consistently less serious CV comorbidity burden and a lower prevalence of severe infection than those with SLE. In contrast, their risk of lymphoma is greater.
PDF
