Janus kinase inhibitors and tumour necrosis factor inhibitors show a favourable safety profile and similar persistence in rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: real-world data from the BIOBADASER registry.

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.

Long-Term Survival of Subcutaneous Biosimilar Tumor Necrosis Factor Inhibitors Compared to Originators: Results From a Multicenter Prospective Registry.

OBJECTIVE: To analyze the long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to the originator molecules in patients with rheumatic diseases, as well as the factors associated with drug discontinuation. METHODS: Retrospective analysis of BIOBADASER, the Spanish multicenter prospective registry of patients with rheumatic disease receiving biologic and targeted disease-modifying antirheumatic drugs. Patients who started etanercept (ETN) or adalimumab (ADA) from January 2016 to October 2023 were included. The survival probabilities of biosimilars and originators were compared using Kaplan-Meier estimating curves. To identify factors associated with differences in the retention rates, hazard ratios (HR) were estimated using Cox regression models for all and specific causes (inefficacy or adverse events [AEs]) of discontinuation. RESULTS: A total of 4162 patients received 4723 treatment courses (2991 courses of ADA and 1732 courses of ETN), of which 722 (15.29%) were with originator molecules and 4001 (84.71%) were with biosimilars. The originators were more frequently discontinued than biosimilars (53.32% vs 33.37%, respectively). The main reason for discontinuation was inefficacy (60.35% of the treatments). The risk of overall discontinuation was lower for biosimilars (adjusted HR 0.84, 95% CI 0.75-0.95). Female sex, obesity, and second or later treatment lines increased the risk of discontinuation, whereas disease duration and the use of concomitant methotrexate were associated with a greater survival. When assessing cause-specific reasons of discontinuation, excluding nonmedical switching, the results from the crude and adjusted analyses showed no significant differences in the retention rate between biosimilars and originators. CONCLUSION: No significant differences were found between treatments in long-term survival due to inefficacy or AEs.

Cardiovascular mortality and cardiovascular event rates in patients with inflammatory rheumatic diseases in the CARdiovascular in rheuMAtology (CARMA) prospective study-results at 5 years of follow-up.

OBJECTIVES: To determine cardiovascular (CV) mortality and incidence of the first CV event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD) after 5 years of follow-up. METHODS: This is an analysis of the CARdiovascular in rheMAatology (CARMA) study after 5 years of follow-up. It includes patients with RA (n = 775), AS (n = 738) and PsA (n = 721), and individuals without CIRD (n = 677) attending outpatient rheumatology clinics from 67 public hospitals in Spain. Descriptive analyses were performed for the CV mortality at 5 years. The Systematic COronary Risk Evaluation (SCORE) function at 5 years was calculated to determine the expected risk of CV mortality. Poisson models were used to estimate the incidence rates of the first CVE. Hazard ratios of the risk factors involved in the development of the first CVE were evaluated using the Weibull proportional hazard model. RESULTS: Overall, 2382 subjects completed the follow-up visit at 5 years. Fifteen patients died due to CVE. CV deaths observed in the CIRD cohort were lower than that predicted by SCORE risk charts. The highest incidence rate of CVE [7.39 cases per 1000 person-years (95% CI 4.63, 11.18)] was found in PsA patients. However, after adjusting for age, sex and CV risk factors, AS was the inflammatory disease more commonly associated with CVE at 5 years [hazard ratio 4.60 (P =0.02)], compared with those without CIRD. CONCLUSIONS: Cardiovascular mortality in patients with CIRD at 5 years of follow-up is lower than estimated. Patients with AS have a higher risk of developing a first CVE after 5 years of follow-up.

Association of apolipoprotein B/apolipoprotein A1 ratio and cardiovascular events in rheumatoid arthritis: results of the CARMA study.

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.

Hyperlipoproteinaemia(a) in patients with spondyloarthritis: results of the Cardiovascular in Rheumatology (CARMA) project.

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.

Incidence of first cardiovascular event in Spanish patients with inflammatory rheumatic diseases: prospective data from the CARMA project.

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.

Factors associated with long-term retention of treatment with golimumab in a real-world setting: an analysis of the Spanish BIOBADASER registry.

The retention rate of a biological drug (percentage of patients remaining on treatment over time) provides an index of a drug's overall effectiveness. The golimumab retention rate as first-line biological therapy was high in clinical trial extensions lasting 5 years. Real-world studies also indicate good retention rates but have been of shorter duration. The probability of retention with golimumab treatment was assessed, as any line of anti-tumor necrosis factor-alpha therapy, for up to 5 years in patients with rheumatoid arthritis (RA), axial spondyloarthritis (SpA) or psoriatic arthritis (PsA), associated factors were analyzed. A retrospective database analysis of the Spanish registry of patients with rheumatic disorders receiving biological drugs (BIOBADASER) was performed. Among 353 patients, 29.8% had RA, 41.6% SpA and 28.6% PsA. Golimumab was the first biological drug in 40.1% of patients, second in 30.1% and third/later in 29.8%. The overall probability of retention of golimumab at years 1, 2, 3, 4 and 5 was 85.9% (95% confidence interval 81.4-89.5%), 73.7% (67.1-79.1%), 68.5% (60.5-75.1%), 60.6% (50.2-69.5%) and 57.1% (44.9-67.5%), respectively. Retention was similar across indications (p = 0.070) but was greater when golimumab was used as the first biological agent compared with later therapy lines (p < 0.001). Factors associated with higher retention of golimumab treatment (Cox regression) were use as a first-line biological and concomitant methotrexate treatment; corticosteroid need was associated with lower retention. The long-term probability of golimumab retention was high in this real-world study of patients with rheumatic diseases, especially when used as the first biological drug.

Variability in the prescription of biological drugs in rheumatoid arthritis in Spain: a multilevel analysis.

To describe variability in the prescription of biologics (B-DMARDs) for patients with rheumatoid arthritis (RA) in hospitals in Spain, and to explore which characteristics of the patient, the doctor and the hospital are associated with this variability. Cross-sectional multicentric study in 46 rheumatology services of the National Health System. Medical records of 1188 randomly selected patients were reviewed. The association of each variable with B-DMARD prescription was analyzed using simple logistic regressions. Multilevel logistic regression models were created to analyze variability among centers. 36.8% of patients had received B-DMARD. The proportion of patients being treated with B-DMARDs varied between 3.6 and 71.4% depending on the center. Association of prescription of B-DMARD with patient age (OR = 0.958, 95% CI = 0.947-0.968, p < 0.001), longer disease duration (OR = 1.05, 95% CI = 1.032-1.069, p < 0.001), higher CRP levels (OR = 1.022, 95% CI = 1.003-1.042, p = 0.023), and higher number of hospitalizations (OR = 1.286, 95% CI = 1.145-1.446, p < 0.001) was observed. With regard to the center characteristics, the existence of telephone consultations (OR = 1.438, 95% CI = 1.037-1.994, p = 0.03) and the number of beds (OR = 1.045, 95% CI = 1.001-1.091, p = 0.044) were positively associated with prescription of B-DMARDs. Patient variables explained 34.04% of the variability among centers. By adjusting for patient and hospital characteristics, it went up to 83.71%. There is variability in the prescription of B-DMARDs for patients with RA among hospitals which is associated, to a greater extent, with the center characteristics. B-DMARDs prescription could be partly explained by other factors not covered by the current study including the provider's attitudes towards biologics and other hospital characteristics.

Fibromyalgia prevalence and associated factors in primary Sjögren's syndrome patients in a large cohort from the Spanish Society of Rheumatology registry (SJOGRENSER).

OBJECTIVES: To assess fibromyalgia (FM) prevalence in a large cohort of primary Sjögren's syndrome patients (pSS) from a National Database. METHODS: Data included in the national retrospective register of pSS patients of the Spanish Society of Rheumatology (SJOGRENSER) were analysed. RESULTS: 437 pSS patients were included and a 14.6% of FM prevalence was found. FM-pSS patients significantly showed more constitutional, fatigue and arthralgia symptoms, splenomegaly, genital, skin and ear involvement and dyslipidaemia (p<0.05), as well as higher ESSPRI and SSDAI scores (p<0.01). Several symptomatic treatments were more frequently used in FM-pSS patients. No differences were observed in laboratory markers, imaging techniques or histologic inflammatory findings. Patients with FM showed statistically more fatigue than pSS without FM. In the multivariate logistic regression analysis several features were associated to pSS-FM patients. CONCLUSIONS: We show data on a reliable prevalence of FM in pSS patients and its multiple associated factors along with the presence of higher disease activity scores than patients who did not show FM. The presence of fatigue, arthralgia, constitutional symptoms and dyslipidaemia were more likely to coexist in pSS-FM patients.

Juvenile- and adult-onset systemic lupus erythematosus: a comparative study in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER).

OBJECTIVES: We aimed to describe juvenile-onset systemic lupus erythematosus (jSLE) features and to establish its differences compared to adult-onset SLE (aSLE) from a large national database. METHODS: Data from patients (≥4 ACR criteria) included in Spanish Society of Rheumatology Lupus Registry (RELESSER) were analysed. Sociodemographic, clinical, serological, activity, treatment, cumulative damage, comorbidities and severity data were collected. Patients with disease onset <18 years were described and compared to those with disease onset ≥18 years. RESULTS: We reviewed 3,428 aSLE patients (89.6% women) and 484 jSLE patients (89.8% girls), 93% Caucasian (both groups). Mean age at diagnosis was 38.1±14 and 16.6±6.3 years (p<0.001) and mean age at the end of follow-up was 48.8±14.3 and 31.5±30 years (p<0.001), respectively. jSLE showed significantly more clinical (including lymphadenopathy, fever, malar rash, mucosal ulcers, pericarditis, pleuritis, Raynaud's phenomenon, lupus nephritis, recurrent nephritis, histologic nephritis changes, thrombocytopenia, haemolytic anaemia, thrombotic thrombocytopenic purpura, seizures, lupus headache and organic brain syndrome) and immunological (a-dsDNA and a-Sm antibodies, hypocomplementaemia) involvement than did aSLE, except for secondary Sjögren's syndrome, a-Ro antibodies, fibromyalgia and osteoporosis. jSLE also showed more SLE family history, longer diagnosis delay, higher SLEDAI and Katz scores, but lower Charlson scores than aSLE. Several specific domains were more frequently involved in SLICC/ACR DI in jSLE. jSLE patients more frequently underwent all SLE-related treatment and procedures, as well as dialysis and kidney transplantations. CONCLUSIONS: jSLE shares many clinical and serological features with aSLE. However, jSLE patients typically manifested more activity, severity, cumulative damage in certain areas, than their aSLE counterparts.

Development of an activity disease score in patients with uveitis (UVEDAI).

To develop a disease activity index for patients with uveitis (UVEDAI) encompassing the relevant domains of disease activity considered important among experts in this field. The steps for designing UVEDAI were: (a) Defining the construct and establishing the domains through a formal judgment of experts, (b) A two-round Delphi study with a panel of 15 experts to determine the relevant items, (c) Selection of items: A logistic regression model was developed that set ocular inflammatory activity as the dependent variable. The construct "uveitis inflammatory activity" was defined as any intraocular inflammation that included external structures (cornea) in addition to uvea. Seven domains and 15 items were identified: best-corrected visual acuity, inflammation of the anterior chamber (anterior chamber cells, hypopyon, the presence of fibrin, active posterior keratic precipitates and iris nodules), intraocular pressure, inflammation of the vitreous cavity (vitreous haze, snowballs and snowbanks), central macular edema, inflammation of the posterior pole (the presence and number of choroidal/retinal lesions, vascular inflammation and papillitis), and global assessment from both (patient and physician). From all the variables studied in the multivariate model, anterior chamber cell grade, vitreous haze, central macular edema, inflammatory vessel sheathing, papillitis, choroidal/retinal lesions and patient evaluation were included in UVEDAI. UVEDAI is an index designed to assess the global ocular inflammatory activity in patients with uveitis. It might prove worthwhile to motorize the activity of this extraarticular manifestation of some rheumatic diseases.

Synthetic disease-modifying antirheumatic drug prescribing variability in rheumatoid arthritis: a multilevel analysis of a cross-sectional national study.

The objective of this study was to describe the variability in the prescription of csDMARDs for the treatment of RA between centers in Spain and to explore how this variability relates to demographic, disease, physician, and institutional characteristics. A cross-sectional nationwide study was carried out to examine data from 1352 patients. Multilevel logistic regression with two levels was performed to assess the relationships between individual and disease-related factors, as well as physician and hospital characteristics, vis-à-vis csDMARD prescription. Having three or more comorbidities (OR 0.353 [0.173-0.721]), disease duration (OR 0.321 [0.174-0.595]), and the existence of an early-arthritis unit (OR 0.552 [0.335-0.910]) were negatively associated with the prescription of one csDMARD versus nonprescription; contrary, the presence of rheumatoid factor (OR 1.909, 95 % CI [1.181-3.086]) was positively associated. On the other hand, while corticoid intake (OR 1.561 [1.088-2.240]), the maximum number of painful joints, and the presence of nursing consultation (OR 1.626 [1.078-2.452]) were positively associated with the prescription of multiple csDMARDs versus one csDMARD, patient's age (OR 0.984 [0.974-0.995]) and disease duration (OR 0.669 [0.462-0.968]) were negatively associated. Despite all these, variability in the prescription of csDMARDs between hospitals remained statistically significant after adjusting for these individual and hospital characteristics. Within the emAR II study, there was a marked variation in the number of csDMARDs prescribed between hospitals. The reasons for these variations remain unclear and cannot be solely related to disease or center characteristics.

Early identification of golimumab-treated patients with higher likelihood of long-term retention.

Background: The early identification of patients' profiles most likely to respond to and maintain long-term therapy with a biological drug can have clinical and cost-effectiveness implications. Objectives: To evaluate the utility of an innovative approach for early identification of patient profiles associated with long-term persistence of golimumab, a tumour necrosis factor inhibitor, in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (SpA) under real-world conditions. Design: Retrospective non-interventional database analysis. Methods: Kaplan-Meier curves of golimumab retention over 8 years from the BIOBADASER registry, overall and by indication, were analysed using a novel approach (a two-phase decay model) to identify the point at which the golimumab retention curve shifted from rapid (indicating high golimumab discontinuation rate) to slow decay (low discontinuation rate). Factors associated with golimumab retention at these time points were identified using Cox regression, and retention rates for different patient profiles were calculated. Results: 885 patients were included. The golimumab retention curve shifted from rapid to slow decay at month 10 for the overall population (retention rate: 73.4%), at month 24 for RA patients (retention: 45.0%), and at month 8 for SpA, including axial SpA and PsA (81.6%). Factors associated with golimumab discontinuation at these early points were, overall, similar to those previously identified at year 8 (RA diagnosis, golimumab as second- or third-line of biological therapy, disease activity over the median and treatment with corticosteroids at golimumab initiation, advanced age [in RA], and female gender [in SpA]). Conclusion: With this novel approach, the factors associated with long-term retention were identified in the initial period of rapid discontinuation of golimumab.

Impact of multimorbidity on the first ts/bDMARD effectiveness and retention rate after two years of follow-up in patients with rheumatoid arthritis from the BIOBADASER registry.

BACKGROUND: Patients with Rheumatoid Arthritis (RA) have a higher prevalence of comorbidities compared to the general population. However, the implications of multimorbidity on therapeutic response and treatment retention remain unexplored. OBJECTIVES: (a) To evaluate the impact of multimorbidity on the effectiveness of the first targeted synthetic or biologic disease-modifying antirheumatic drug (ts/bDMARD), in patients with RA after 2-year follow-up; (b) to investigate the influence of multimorbidity on treatment retention rate. METHODS: Patients with RA from the BIOBADASER registry exposed to a first ts/bDMARDs were included. Patients were categorized based on multimorbidity status at baseline, defined as a Charlson Comorbidity index (CCI) score ≥ 3. A linear regression model, adjusted for sex and age, was employed to compare the absolute DAS28 score over time after ts/bDMARD initiation between the two groups. The Log-Rank test and Kaplan-Meier curve were used to compare the retention rates of the first ts/bDMARD between the groups. RESULTS: A total of 1128 patients initiating ts/bDMARD were included, with 107 (9.3%) exhibiting multimorbidity. The linear regression model showed significantly higher DAS28 (beta coefficient 0.33, 95%CI:0.07-0.58) over a two-year period in patients with multimorbidity, even after adjusting for age and sex. Finally, no differences in the ts/bDMARD retention rate were found between groups (median 6.94-6.96 years in CCI < 3 vs. 5.68-5.62 in CCI ≥ 3; p = 0.610). CONCLUSIONS: Multimorbidity in patients with RA was associated with greater DAS28 scores within the first two years after ts/bDMARD initiation, in comparison with patients without multimorbidity. A slightly shorter retention rate was found in patients with multimorbidity, although the difference was non-significant.

Use of risk chart algorithms for the identification of psoriatic arthritis patients at high risk for cardiovascular disease: findings derived from the project CARMA cohort after a 7.5-year follow-up period.

OBJECTIVE: To assess the predictive value of four cardiovascular (CV) risk algorithms for identifying high-risk psoriatic arthritis (PsA) patients. METHODS: Evaluation of patients with PsA enrolled in the Spanish prospective project CARdiovascular in RheuMAtology. Baseline data of 669 PsA patients with no history of CV events at the baseline visit, who were followed in rheumatology outpatient clinics at tertiary centres for 7.5 years, were retrospectively analysed to test the performance of the Systematic Coronary Risk Assessment (SCORE), the modified version (mSCORE) European Alliance of Rheumatology Associations (EULAR) 2015/2016, the SCORE2 algorithm (the updated and improved version of SCORE) and the QRESEARCH risk estimator version 3 (QRISK3). RESULTS: Over 4790 years of follow-up, there were 34 CV events, resulting in a linearised rate of 7.10 per 1000 person-years (95% CI 4.92 to 9.92). The four CV risk scales showed strong correlations and all showed significant associations with CV events (p<0.001). SCORE, mSCORE EULAR 2015/2016 and QRISK3 effectively differentiated between low and high CV risk patients, although the cumulative rate of CV events observed over 7.5 years was lower than expected based on the frequency predicted by these risk scales. Additionally, model improvement was observed when combining QRISK3 with any other scale, particularly the combination of QRISK3 and SCORE2, which yielded the lowest Akaike information criterion (411.15) and Bayesian information criterion (420.10), making it the best predictive model. CONCLUSIONS: Risk chart algorithms are very useful for discriminating PsA at low and high CV risk. An integrated model featuring QRISK3 and SCORE2 yielded the optimal synergy of QRISK3's discrimination ability and SCORE2's calibration accuracy.

Combined use of QRISK3 and SCORE2 increases identification of ankylosing spondylitis patients at high cardiovascular risk: Results from the CARMA Project cohort after 7.5 years of follow-up.

OBJECTIVE: To establish the predictive value of the QRESEARCH risk estimator version 3 (QRISK3) algorithm in identifying Spanish patients with ankylosing spondylitis (AS) at high risk of cardiovascular (CV) events and CV mortality. We also sought to determine whether to combine QRISK3 with another CV risk algorithm: the traditional SCORE, the modified SCORE (mSCORE) EULAR 2015/2016 or the SCORE2 may increase the identification of AS patients with high-risk CV disease. METHODS: Information of 684 patients with AS from the Spanish prospective CARdiovascular in ReuMAtology (CARMA) project who at the time of the initial visit had no history of CV events and were followed in rheumatology outpatient clinics of tertiary centers for 7.5 years was reviewed. The risk chart algorithms were retrospectively tested using baseline data. RESULTS: After 4,907 years of follow-up, 33 AS patients had experienced CV events. Linearized rate=6.73 per 1000 person-years (95 % CI: 4.63, 9.44). The four CV risk scales were strongly correlated. QRISK3 correctly discriminated between people with lower and higher CV risk, although the percentage of accumulated events over 7.5 years was clearly lower than expected according to the risk established by QRISK3. Also, mSCORE EULAR 2015/2016 showed the same discrimination ability as SCORE, although the percentage of predicted events was clearly higher than the percentage of actual events. SCORE2 also had a strong discrimination capacity according to CV risk. Combining QRISK3 with any other scale improved the model. This was especially true for the combination of QRISK3 and SCORE2 which achieved the lowest AIC (406.70) and BIC (415.66), so this combination would be the best predictive model. CONCLUSIONS: In patients from the Spanish CARMA project, the four algorithms tested accurately discriminated those AS patients with higher CV risk and those with lower CV risk. Moreover, a model that includes QRISK3 and SCORE2 combined the best discrimination ability of QRISK3 with the best calibration of SCORE2.

Interobserver Reliability and Sensitivity to Change of a Composite Ocular Inflammatory Activity Index: UVEDAI©.

INTRODUCTION: This was a multicenter, prospective, longitudinal, observational study involving eight Spanish tertiary hospitals to determine the interobserver reliability of an uveitis disease activity index, (UVEDAI) and assess its sensitivity to change in patients with receiving pharmacologic treatment. METHODS: Patients aged ≥ 18 years diagnosed with active noninfectious uveitis were included. A complete baseline assessment was performed by two ophthalmologists who determined ocular inflammatory activity using the UVEDAI index independently of each other. The principal ophthalmologist made a new visit at 4 weeks to determine the change in inflammatory activity. The interobserver reliability analysis was performed by calculating the intraclass correlation coefficient (ICC), with the values of the variables and the UVEDAI obtained by both ophthalmologists in the more active eye at the baseline visit. Sensitivity to change in the UVEDAI index was assessed at 4 weeks from the start of pharmacologic treatment by determining the clinically relevant change, defined as a change in UVEDAI of ≥ 0.8 points over baseline. The mean change between both measures was compared using the repeated-measures t-test. RESULTS: A total of 111 patients were included. In the interobserver reliability analysis, the ICC for the UVEDAI value was 0.9, and, when compared with the mean UVEDAI values obtained by the ophthalmologists, no statistically significant differences were found (p value > 0.05). As for the sensitivity to change in UVEDAI, statistically significant differences (p value = 0.00) were found for the mean values of the index compared with baseline. In all cases, the index value decreased by > 1 point at the 4-week visit. CONCLUSIONS: The interobserver reliability of the UVEDAI was high in the total sample. Furthermore, the index was sensitive in determining the change in inflammatory activity after treatment. We believe that UVEDAI is a disease activity index that enables objective comparison of results in clinical practice and trials.

Development of a web tool to calculate the cumulative dose of glucocorticoids.

INTRODUCTION: Glucocorticoids are associated with serious side effects related to dosing and time of use. Unfortunately, there is no standard method for determining glucocorticoid exposure, especially in patients undergoing long-term treatment. OBJECTIVE: The aim of this work was to create a free and easy-to-use web application to calculate, in a systematic way, the total cumulative dose of corticosteroids. METHODS: The total cumulative dose is calculated as the sum of all periods of treatment with different doses of corticosteroids, and is expressed as the equivalent dose of prednisone in mg. Glucocorticoid doses during periods in which the available information is missing or incomplete are estimated by systematic assumptions. RESULTS: A simulation exercise using standard patterns of steroid use in polymyalgia rheumatica, and giant cell arteritis showed that even when the period of no information reached 50% of the time, the accuracy of the calculator had a mean absolute percentage error (MAPE)<7%. CONCLUSION: This tool simplifies and standardizes the glucocorticoids cumulative dose calculation, thereby minimizing bias in the assessment of glucocorticoid cumulative dose.

Four-years retention rate of golimumab administered after discontinuation of non-TNF inhibitors in patients with inflammatory rheumatic diseases.

BACKGROUND: In patients with rheumatic diseases, the use of biological (b) or targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) after discontinuation of tumor necrosis factor inhibitors (TNFi) is known to be effective. However, data on the use of TNFi after discontinuation of non-TNFi bDMARDs or tsDMARDs (non-TNFi) are scarce. This study assessed the 4-years golimumab retention in patients with rheumatic diseases when used after discontinuation of non-TNFi. METHODS: Adults with rheumatoid arthritis (RA; n = 72), psoriatic arthritis (PsA; n = 30) or axial spondyloarthritis (axSpA; n = 23) who initiated golimumab after discontinuation of non-TNFi from the Spanish registry of biological drugs (BIOBADASER) were analyzed retrospectively. The retention rate (drug survival or persistence) of golimumab up to 4 years was evaluated. RESULTS: The golimumab retention rate was 60.7% (51.4-68.8) at year 1, 45.9% (36.0-55.2) at year 2, 39.9% (29.8-49.7) at year 3 and 33.4% (23.0-44.2) at year 4. Retention rates did not differ significantly whether golimumab was used as second, third, or fourth/subsequent line of therapy (p log-rank = 0.462). Golimumab retention rates were higher in axSpA or PsA patients than in RA patients (p log-rank = 0.002). When golimumab was administered as third or fourth/subsequent line, the 4-years retention rate after discontinuation of non-TNFi was similar to that after discontinuation of TNFi. CONCLUSION: In patients who discontinued non-TNFi, most of whom received golimumab as third/subsequent line of therapy, one-third of patients remained on golimumab at year 4. Retention rates were higher in patients with axSpA and PsA than in those with RA.

Factors associated with discontinuation of biologics in patients with inflammatory arthritis in remission: data from the BIOBADASER registry.

BACKGROUND: The objectives of this study were to assess the discontinuation of biologic therapy in patients who achieve remission and identify predictors of discontinuation of biologics in patients with inflammatory arthritis in remission. METHODS: An observational retrospective study from the BIOBADASER registry comprising adult patients diagnosed with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA) and receiving 1 or 2 biological disease-modifying drugs (bDMARDs) between October 1999 and April 2021. Patients were followed yearly after initiation of therapy or until discontinuation of treatment. Reasons for discontinuation were collected. Patients who discontinued bDMARDs because of remission as defined by the attending clinician were studied. Predictors of discontinuation were explored using multivariable regression models. RESULTS: The study population comprised 3,366 patients taking 1 or 2 bDMARDs. Biologics were discontinued owing to remission by 80 patients (2.4%): 30 with RA (1.7%), 18 with AS (2.4%), and 32 with PsA (3.9%). The factors associated with a higher probability of discontinuation on remission were shorter disease duration (OR: 0.95; 95% CI: 0.91-0.99), no concomitant use of classic DMARDs (OR: 0.56; 95% CI: 0.34-0.92), and shorter usage of the previous bDMARD (before the decision to discontinue biological therapy) (OR: 1.01; 95% CI: 1.01-1.02); in contrast, smoking status (OR: 2.48; 95% CI: 1.21-5.08) was associated with a lower probability. In patients with RA, positive ACPA was associated with a lower probability of discontinuation (OR: 0.11; 95% CI: 0.02-0.53). CONCLUSIONS: Discontinuation of bDMARDs in patients who achieve remission is uncommon in routine clinical care. Smoking and positive ACPA in RA patients were associated with a lower probability of treatment discontinuation because of clinical remission.