Maite Silva-Díaz

Objectives: The aim of this study was to identify robust predictive markers which may help personalize tapering protocols, minimizing flare risk while optimizing long-term disease management in RA patients. Methods: The OPTIBIO trial (EudraCT 2012–004482-40) was a phase IV, randomized, open-label, non-inferiority study conducted in five hospitals in Spain. RA patients in sustained remission on stable bDMARD therapy were randomized 1:1 to standard care or dose reduction. The primary outcome was to compare the proportion of joint flare between baseline and 12 months by a non-inferiority analysis analysed by the intention-to-treat principle and to identify predictors for flare and sustained remission. Results: A total of 195 patients were randomized: 99 to the control group and 96 to the optimization group. Thirty-nine flares occurred (optimization: 22.7%, control: 17.2%), with a risk difference of −5.5% (95% CI: −16.8% to 5.7%; P = 0.33). Two predictive models were developed: one for flares (AUC: 0.84) including 3v-DAS28-CRP, VAS pain, erosions, systolic blood pressure and haemoglobin, and another for sustained remission (AUC: 0.77) including 3v-DAS28-CRP, age and rheumatoid factor. Adding molecular biomarkers improved AUCs to 0.91 and 0.88, respectively. No significant differences in adverse events were observed. Conclusion: bDMARD dose optimization was not non-inferior to standard therapy on the flare rate but demonstrated similar safety. Predictive models for remission and flares were developed, which may help select patients to ensure safe implementation of this strategy, highlighting the need for personalized treatment. Trial registration: www.clinicaltrialsregister.eu; EudraCT 2012–004482-40

Objective: To evaluate sex-based differences in clinical presentation, vascular phenotype, diagnostic approaches, treatment, adverse events and outcomes among patients with giant cell arteritis (GCA). Methods: We analysed data from all patients diagnosed with GCA between 1 June 2013 and 29 March 2019 across 26 hospitals in Spain. Eligibility criteria included age ≥50 years and diagnosis confirmed by imaging, the 1990 American College of Rheumatology classification criteria, or expert clinical judgment. Results: A total of 1675 patients were included. The extracranial phenotype was more prevalent in women (14.8% vs 9.9%; P = 0.039), while the mixed phenotype was more common in men (17.7% vs 11.7%; P = 0.002). Temporal artery ultrasound was more frequently positive in men (73.5% vs 65.1%; P = 0.025). Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were prescribed more often in women (35.3% vs 28.2%; P = 0.005), while glucocorticoid and tocilizumab use did not differ by sex. Fractures (22.4% vs 10.9%; P = 0.010) and cataracts (6.0% vs 2.8%; P = 0.010) were significantly more frequent in women and men, respectively. Remission rates (23.1% vs 23.8%) and relapse frequencies (19.7% vs 19.3%) were similar between sexes. Mortality was higher in men (13.8% vs 6.6%; P < 0.001). Conclusions: Women more frequently exhibited the extracranial phenotype, required more csDMARDs, and experienced a higher incidence of fractures. In contrast, men more commonly presented with the mixed phenotype, had more cataracts, and showed a higher mortality rate. These findings highlight the importance of integrating sex as a key biological variable in GCA research and clinical management to support more tailored and effective therapeutic strategies.

Objective: To determine whether oral vitamin D supplementation reduces the risk of glucocorticoid (GC)-associated severe adverse events (SAEs) in patients with giant cell arteritis (GCA) included in the Spanish ARTESER registry. Methods: The ARTESER registry collected data from patients diagnosed with GCA across 26 Spanish public hospitals between June 2013 and March 2019. SAEs were defined as fatal, life-threatening, or requiring hospitalization. Patients were categorized according to the use or non-use of oral vitamin D supplements. Incidence rates (IRs) of SAEs were expressed per person-year with 95% confidence intervals (CIs). Cox proportional hazards models assessed vitamin D supplementation and its interaction with cumulative glucocorticoid dose. Results: Of 1568 patients (mean age 76.9 ± 8.1 years; 70.1% women) receiving GC, 120 (7.6%) experienced SAEs (IR 0.039; 95% CI 0.033–0.047). Vitamin D supplementation was documented in 1186 (75.6%) compared with 382 (24.4%) non-supplemented patients. SAE incidence was similar in supplemented (n = 89; 7.5%; IR 0.038, 95% CI 0.030–0.046) and non-supplemented patients (n = 31; 8.1%; IR 0.045, 95% CI 0.031–0.064) (p = 0.387). Multivariable Cox regression showed a significant interaction between vitamin D supplementation and cumulative glucocorticoid dose (interaction term HR 0.90; p = 0.033), consistent with a dose-dependent protective effect. Conclusions: Vitamin D supplementation was not independently associated with a lower incidence of GC-related SAEs, likely due to residual confounding factors. However, the interaction with cumulative GC exposure suggests a modulatory effect. Prospective studies incorporating stratified baseline vitamin D assessments are warranted.

Objective: To investigate the prevalence, timing and risk factors at diagnosis associated with relapses in giant cell arteritis (GCA), with a separate analysis of major and minor relapses. Methods: A retrospective review of patients from the Spanish multicentre GCA registry (ARTESER) was conducted. Relapses were classified using 2018 EULAR definitions. Results: We included 1284 patients with at least one year of follow-up. Twenty-six percent experienced relapses, with cumulative rates of 18.1%, 27.9%, 37.6% and 44.8% at 1, 2, 3 and 4 years, respectively. Multiple relapses were observed in 14.6% of patients during the first year, 10.5% in the second, 9% in the third and 17.8% in the fourth, reflecting the relapsing-remitting nature of GCA. According to EULAR definitions, major relapses represented 26.7% of all recorded relapses and affected 7.6% of patients. Younger age at diagnosis (HR: 0.976, P = 0.004) and a higher total dose of prednisone at the first relapse (HR: 0.998, P = 0.003) were associated with a reduced risk of overall relapses. Severe ischemic complications (HR: 4.126, P < 0.001) and large-vessel (LV) involvement at diagnosis (HR: 1.992, P = 0.024) significantly increased the risk of major relapses, while younger age (HR: 0.970, P = 0.002) was protective against minor relapses. Conclusions: Major relapses are not so uncommon, representing a quarter of all relapses. The presence of severe ischemic complications and LV involvement at diagnosis substantially increase their risk.

Objective: To determine the prevalence and predictive factors of cerebrovascular accidents (CVA) in GCA. Methods: ARTESER is a large Spanish multicentre registry including patients with GCA from across the entire country diagnosed between June 2013 and March 2019 and sponsored by the Spanish Society of Rheumatology. The variables collected at diagnosis were demographics, clinical manifestations (including the occurrence and location of CVA), laboratory, histology and imaging findings. Patients with and without CVA were compared in a bivariate analysis. Multivariate logistic regression was performed to determine potential predictive factors of CVA. Results: A total of 1540 patients with GCA were included for analysis (mean age 77.1 years, 70% females). CVA occurred in 61 (3.96%), of whom 38 (62.3%) involved the vertebrobasilar territory and 21 (34.4%) the carotid territory. The factors associated with CVA were the occurrence of transient ischaemic attack (TIA) [odds ratio (OR) 8.63; 95% CI 2.877–25.86], large vessel (LV) involvement (OR 2.79; 95% CI 1.421–5.465) and the presence of concomitant visual manifestations (OR 2.73; 95% CI 1.427–5.235). The risk of death during follow-up was significantly higher in patients with CVA (18% vs 8.8%; P = 0.014). Patients with CVA received significantly higher mean prednisone (mg) dose at diagnosis (433.9 vs 216; P < 0.001) and cumulative prednisone dose during follow-up (11 203.9 vs 8,194.1; P < 0.001). Conclusion: The prevalence of CVA in patients with GCA is low, but increases the risk of mortality. The presence of TIA, LV involvement and visual manifestations are factors associated with increased risk of CVA.

To compare mortality rates between GCA patients and the general population in Spain, and to identify associated factors influencing mortality. ARTESER, a multicenter registry by the Spanish Society of Rheumatology, includes GCA patients from June 2013 to March 2019. Demographic, clinical, imaging, histological and mortality data were collected retrospectively. Only patients with at least one year of follow-up were included for analysis. The mortality rates were expressed as the number of deaths per 1000 person-years, with 95% confidence interval (CI) by sex and age group. Kaplan-Meier method was performed for survival analysis. The factors influencing mortality were analyzed using Cox regression model. A total of 1200 patients with GCA were analyzed, with a mean (SD) follow-up of 2.18 (1.53) years. The overall five-year cumulative mortality rate (95%CI) was 37.86 (31.75-43.96) per 1000 patients/year. The cumulative mortality rate was significantly higher in males than females (59.04vs29.06; p<0.001). The age- and sex-adjusted cumulative mortality rate was similar to the Spanish general population (19.75vs20.72;p=0.559). In the multivariate analysis, older age (HR 1.11, 95%CI 1.073-1.142) and male sex (HR 1.775, 95%CI 1.214-2.594) were associated with increased mortality. Headache (HR 0.55, 95%CI 0.362-0.843) and high hemoglobin levels (HR 0.85, 95%CI 0.744-0.970) were protective factors against death. The overall five-year age- and sex-adjusted cumulative mortality rate in GCA is similar compared to the general population. Older age and male sex appear to be associated with an increased risk of mortality, whereas headache and high hemoglobin levels might serve as protective factors against death.

Background/Objectives: Imaging studies have transformed the diagnosis of large vessel vasculitis (LVV) involvement in giant cell arteritis (GCA). A positron emission tomography/computed tomography (PET/CT) scan with 18-fluorodeoxyglucose (18F-FDG) has emerged as a valuable tool for assessing LVV. We aimed to determine the utility of an 18F-FDG-PET/CT scan in detecting LVV in GCA in the ARTESER registry. Methods: The ARTESER study is a large multicenter, retrospective, longitudinal, and observational study, promoted by the Spanish Society of Rheumatology. It included patients newly diagnosed with GCA across 26 tertiary hospitals from 1 June 2013 to 29 March 2019. Patients with a diagnosis of incidental GCA were included if they fulfilled specific criteria, including the ACR 1990 criteria, positive imaging examinations, or the expert clinical opinion of investigators. Differences between patients with positive and negative 18F-FDG-PET/CT scan results were analyzed using a bivariate model. A regression model assessed associations in patients with a positive scan, and the predictive capacity of the cumulative dose of glucocorticoids (GC) on PET scan outcomes was evaluated using ROC curve analysis. Results: Out of 1675 GCA patients included in the registry, 377 met the inclusion criteria of having an 18F-FDG-PET/CT scan. The majority were diagnosed with a cranial GCA phenotype, and 65% had LVV. The thoracic aorta was the most frequently affected. Cardiovascular disease, diabetes, and older age had a negative association with a positive scan outcome. The OR for having a positive 18F-FDG-PET/CTC scan was lower as the number of days increased. Depending on the cumulative dosage of the GC, the 18F-FDG-PET/CT scan showed an AUC of 0.74, with a Youden index > 60 mg/day. Conclusions: Younger patients showed a higher probability of presenting LVV as detected by the 18F-FDG-PET/CT scan. The timing of the examination and the cumulative dosage of the GC influenced the likelihood of a positive result, with earlier tests being more likely to detect inflammation.

Objective This study aimed to estimate the incidence of giant cell arteritis (GCA) in Spain and to analyse its clinical manifestations, and distribution by age group, sex, geographical area and season. Methods We included all patients diagnosed with GCA between 1 June 2013 and 29 March 2019 at 26 hospitals of the National Health System. They had to be aged ≥50 years and have at least one positive results in an objective diagnostic test (biopsy or imaging techniques), meet 3/5 of the 1990 American College of Rheumatology classification criteria or have a clinical diagnosis based on the expert opinion of the physician in charge. We calculated incidence rate using Poisson regression and assessed the influence of age, sex, geographical area and season. Results We identified 1675 cases of GCA with a mean age at diagnosis of 76.9±8.3 years. The annual incidence was estimated at 7.42 (95% CI 6.57 to 8.27) cases of GCA per 100 000 people ≥50 years with a peak for patients aged 80–84 years (23.06 (95% CI 20.89 to 25.4)). The incidence was greater in women (10.06 (95% CI 8.7 to 11.5)) than in men (4.83 (95% CI 3.8 to 5.9)). No significant differences were found between geographical distribution and incidence throughout the year (p=0.125). The phenotypes at diagnosis were cranial in 1091 patients, extracranial in 337 patients and mixed in 170 patients. Conclusions This is the first study to estimate the incidence of GCA in Spain at a national level. We found a predominance among women and during the ninth decade of life with no clear variability according to geographical area or seasons of the year.

Objective: Axial osteoarthritis (OA) is a common cause of back and neck pain, however, few studies have examined its prevalence. The aim was to estimate the prevalence and the characteristics of symptomatic axial OA in Spain. Methods: EPISER2016 is a cross-sectional multicenter population-based study of people aged 40 years or older. Subjects were randomly selected using multistage stratified cluster sampling. Participants were contacted by telephone to complete rheumatic disease screening questionnaires. Two phenotypes were analyzed, patients with Non-exclusive axial OA (NEA-OA) and Exclusive axial OA (EA-OA). To calculate the prevalence and its 95% confidence interval (CI), the sample design was considered and weighting was calculated according to age, sex and geographic origin. Results: Prevalence of NEA-OA by clinical or clinical-radiographic criteria was 19.17% (95% CI: 17.82–20.59). The frequency of NEA-OA increased with age (being 3.6 times more likely in patients aged 80 s or more than in those between 40 and 49 years) and body mass index. It was significantly more frequent in women, as well as in the center of Spain. It was less frequent in those with a higher level of education. Lumbar OA was more frequent than cervical OA. This difference grew with increasing age and was not associated with gender. It was also greater in overweight and obese subjects. Conclusions: This is the first study on the prevalence of axial OA phenotypes in Europe describing the associated socio-demographic, anthropometric, and lifestyle variables.