Real-world persistence of initial targeted therapy strategy in monotherapy versus combination therapy in patients with chronic inflammatory arthritis.

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.

Depression and anxiety in systemic lupus erythematosus: A case-control study on prevalence and associated factors in a single-center cohort.

OBJECTIVES: To evaluate the prevalence of self-perceived depression and anxiety in patients with systemic lupus erythematosus (SLE) and to explore associated factors. METHODS: Cross-sectional study of unselected patients with SLE (ACR-97 criteria) and controls with chronic inflammatory rheumatic diseases. Both completed the Hospital Anxiety and Depression Scale (HADS). Demographic and clinical characteristics, comorbidity, and treatments were collected, and a multivariate analysis was performed to explore factors associated with depression and anxiety in SLE. RESULTS: The study population comprised 172 patients and 215 controls. Women accounted for 93% of the patients with SLE. Fibromyalgia was recorded in 12.8% and a history of depression in 17%. According to HADS, 37.2% fulfilled the diagnostic criteria for depression and 58.7% those for anxiety; prevalence was similar in the controls (32.6% and 55.1%, respectively). Up to a third of patients with self-perceived depression were not receiving antidepressants. There was no concordance between a previous history of depression and current depression. In the multivariate model, current depression was associated with single marital status (OR 2.69; 95% CI: 1.17-6.42; p = .022), fibromyalgia (7.69; 2.35-30.72; p = .001), smoking (3.12; 1.24-8.07; p = .016), severity of SLE (0.76; 0.6-0.94; p = .016), and organ damage (1.27; 1.01-1.61; p = .042). Current anxiety was only associated with fibromyalgia (3.97; 1.21-17.98; p = .036). CONCLUSIONS: Depression and anxiety are most likely underdiagnosed in SLE. Prevalence appears to be similar to that of other chronic inflammatory rheumatic diseases. Anxiety is associated with fibromyalgia, while depression is also associated with single marital status, smoking, organ damage, and severity of SLE.

Proprotein convertase subtilisin/kexin type 9 in the dyslipidaemia of patients with axial spondyloarthritis is related to disease activity.

OBJECTIVE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism and has been linked to cardiovascular (CV) risk. The purpose of the present study was to examine whether PCSK9 levels are related to abnormalities in the lipid profile and the development of atherosclerosis that occurs in patients with axial SpA (axSpA). METHODS: We performed a cross-sectional study that encompassed 545 individuals; 299 patients with axSpA and 246 statin use-matched controls. PCSK9 and standard lipid profiles were analysed in patients and controls. Carotid intima-media thickness (cIMT) and carotid plaques were assessed in patients. A multivariable analysis, adjusted for standard CV risk factors, was performed to evaluate the influence of PCSK9 on axSpA-related dyslipidaemia and subclinical carotid atherosclerosis. RESULTS: Total cholesterol, high-density lipoprotein and low density lipoprotein cholesterol, lipoprotein (a) and apolipoprotein A1 were significantly lower in axSpA patients than controls. PCSK9 serum levels [ß coefficient -44 ng/dl (95% CI -60, -27), P = 0.000] were also downregulated in axSpA patients after fully multivariable adjustment. ASDAS-CRP was found to be independently and significantly related to PCSK9 [ß coefficient 10 ng/dl (95% CI 1, 18), P = 0.023] after analysing fully adjusted models that took age, sex and the rest of the lipid profile molecules into account. Whereas patients taking prednisone showed higher serum levels of PCSK9 [55 ng/ml (95% CI 24, 8), P = 0.001], those under anti-TNF-α therapies exhibited lower levels [ß coefficient -26 ng/ml (95% CI -43, -9], P = 0.003]. CONCLUSION: PCSK9 is downregulated in patients with axSpA. Disease activity is positive and significantly related to PSCK9. Anti-TNF-therapy yields a reduction in PCSK9 serum levels.

Impaired HDL cholesterol efflux capacity in systemic lupus erythematosus patients is related to subclinical carotid atherosclerosis.

OBJECTIVES: Lipid profiles appear to be altered in SLE patients due to disease activity and inflammation. Cholesterol efflux capacity (CEC) is the ability of high-density lipoprotein cholesterol to accept cholesterol from macrophages. CEC has been linked to cardiovascular events in the general population and is impaired in SLE patients. The aim of this study was to establish whether CEC is related to subclinical carotid atherosclerosis in SLE patients. METHODS: The present report is of a cross-sectional study that encompassed 418 individuals: 195 SLE patients and 223 controls. CEC, using an in vitro assay, and lipoprotein serum concentrations were assessed in patients and controls. Carotid intima-media thickness and carotid plaques were evaluated in SLE patients. A multivariable analysis was performed to study the relationship of CEC to SLE-related data, lipid profile and subclinical carotid atherosclerosis. RESULTS: CEC was downregulated in SLE patients [8.1 (4.2) % vs 16.9 (10.4) %, P = 0.004). This occurred independently of traditional cardiovascular risk factors, statin use or other variations in the lipid profile related to the disease. Traditional cardiovascular risk factors, both in patients and controls, and SLE-related data such as activity, severity or damage were not associated with CEC. After multivariable regression analysis including lipid profile-related molecules, CEC was inversely and independently associated with the presence of carotid plaques in SLE patients [odds ratio 0.87 (95% CI: 0.78, 0.97), P = 0.014]. CONCLUSION: CEC is impaired in SLE patients independently of other inflammation-related lipid profile modifications that occur during the disease. CEC is associated with carotid plaques in SLE patients.

"There is something you must see": breaking down the remission concept in rheumatoid arthritis from a rheumatologist's perspective.

OBJECTIVES: To explore the remission concept in rheumatoid arthritis (RA) and the implications of the existing definitions when applied to clinical practice among rheumatologists with different profiles. METHODS: A qualitative study through focus groups was conducted. Three focus groups were organised from February to March 2016. Each group was composed of rheumatologists with extensive clinical experience with different profiles; experts in basic research (RBR), experts in imaging techniques research (RIR), and experts in clinical research (RCR). The data was collected with audio recording. Verbatim transcriptions of the audio files were made, and a subsequent reflexive thematic analysis assisted by ATLAS.ti (GmbH, Berlin, v. 7) software was performed. RESULTS: From the reflexive thematic analysis, three main themes were generated: (1) remission limitations, (2) instruments or measures to assess remission, and (3) a new definition of remission. Rheumatologists mentioned frequently that the following variables should be considered when developing a new remission definition: inflammatory activity, calprotectin, psychological variables, sex, disease stage, and sociocultural factors. Contrary to what could be expected, all groups acknowledged that their research field could contribute with domains for a gold standard remission instrument, but not in a hierarchical arrangement of importance. The dissonance existing in the entire remission evaluation process was outlined: remission in clinical practice versus remission in clinical trials, remission following the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean versus Musculoskeletal Ultrasound (US) remission, and remission from the rheumatologist's point of view versus the patient's point of view. CONCLUSIONS: Currently, rheumatologists would not accept a domain as more important than others in remission. Our suggestion is, not to generate a universal definition of remission - one that could cover all aspects - but rather to develop definitions of remission for the different settings that could be pondered by the patient's perspective.

Tobacco smoking is an independent factor associated with retinal damage in systemic lupus erythematosus: a cross-sectional and retrospective study.

To analyze the influence of tobacco smoking on systemic lupus erythematosus (SLE) clinical features and damage. Cross-sectional and retrospective, case-control study comparing SLE patients with and without tobacco exposure. Cumulative clinical data and comorbidities were collected, and severity (Katz index) and damage (SLICC/ACR damage index) (SDI) indices were calculated. Pack-years (PY) was used to estimate lifetime tobacco exposure. A logistic regression was carried out to explore the impact of tobacco use on retinal damage. 216 patients were included. The mean age was 49 years (± 12.7), 93% were females, and median disease duration was 17 years [interquartile range (IQR):9-25]. Fifty-three percent of patients were smokers at some point. The median PY was 13 (IQR: 6-20.5). Only 54.8% of active smokers recalled having been informed of the negative effects of smoking, versus 83.3% of never smokers (< 0.001). In a bivariant analysis, an association between tobacco use at any time and discoid lupus [OR: 3.5(95%CI 1.5-8.9); p = 0.002] photosensitivity [OR: 2.06(95%CI 1.16-3.7); p = 0.01] and peripheral arteriopathy (p = 0.007) was found. Considering SDI item by item, a significant association with retinal damage, adjusted for age [OR: 1.03(95%CI 1-1.07); p = 0.04], was found. Using PYs, an association was found with discoid lupus (p = 0.01), photosensitivity (p = 0.03) and peripheral arteriopathy (p = 0.01), global SDI > 0 (p = 0.002) and retinal damage (p = 0.02). In a multivariate analysis exploring factors associated with retinal damage, any previous smoking history and SDI remained associated with retinal damage. Tobacco smoking is associated with cutaneous manifestations and damage and is an independent predictor of retinal damage in SLE patients.

The EJES-3D tool for personalized prescription of exercise in axial spondyloarthritis through multimedia animations: pilot study.

To develop and evaluate a web application based on multimedia animations, combined with a training program, to improve the prescription of exercises in spondyloarthritis (SpA). After a review of exercises included in the main clinical trials and recommendations of international societies, a multidisciplinary team-rehabilitators, rheumatologists, physiotherapists, computer scientists and graphic designers-developed a web application for the prescription of exercises (EJES-3D). Once completed, this was presented to 12 pairs of rehabilitators-rheumatologists from the same hospital in a workshop. Knowledge about exercise was tested in rheumatologists before and 6 months after the workshop, when they also evaluated the application. The EJES-3D application includes 38 multimedia videos and allows prescribing predesigned programs or customizing them. A patient can consult the prescribed exercises at any time from a device with internet connection (mobile, tablet, or computer). The vast majority of the evaluators (89%) were satisfied or very satisfied and considered that their expectations regarding the usefulness of the web application had been met. They highlighted the ability to tailor exercises adapted to the different stages of the disease and the quality and variety of the videos. They also indicated some limitations of the application and operational problems. The EJES-3D tool was positively evaluated by experts in SpA, potentially the most demanding group of users with the most critical capacity. This allows a preliminary validation of the contents, usefulness, and ease of use. Analyzing and correcting the errors and limitations detected is allowing us to improve the EJES-3D tool.

Exploring the remission concept in rheumatoid arthritis with patients and rheumatologists: time for a new approach?

OBJECTIVES: To explore the remission concept in rheumatoid arthritis (RA) and to compare remission definitions and related concepts between rheumatologists and patients with the purpose of identifying similarities and disparities to comprehend the different perspectives of the disease. METHODS: This was a qualitative study of discourse and content analysis through focus groups, conducted from February to March 2016. Four focus groups were set up, each one with different interests: rheumatologists involved in basic research (BR), rheumatologists with high specialisation in imaging techniques (IR), clinical rheumatologists (CR), and patients (PA). RESULTS: There is no consensus in a remission definition in RA; differences exist between-groups, rheumatologists and patients value remission differently, and there are discrepancies within the group of rheumatologists. Rheumatologists highlight quantifiable objective parameters, in contrast, patients did not consider objective measures as the best instruments, and they prefer subjective measures of remission. The data confirmed the existence of two sources of knowledge of the disease, technical (physicians) and experiential (patients). These sources of knowledge should concur in order to establish new remission criteria well-adjusted to reality. CONCLUSIONS: The lack of consensus between key groups implicated in defining remission and remission criteria suggests a new strategy for its operational definition. Our group proposes that subjects with a balance between experiential and technical knowledge, should be the ones in charge of this assignment.

Factors associated with the intensification of treatment in rheumatoid arthritis in clinical practice.

The aim of the present study was to analyse the patterns of treatment adjustment in rheumatoid arthritis (RA) patients with active disease in routine clinical care. This was a cross-sectional study of consecutive patients with RA conducted in five hospitals. Activity scales (DAS28-ESR) and function (HAQ) were measured, as well as whether ultrasound was performed as part of the assessment. Treatment decision (no changes/reduction/intensification) and time to the next scheduled visit were the outcomes variables. Associated factors were analysed by multilevel regression models. A total of 343 patients were included (77 % women, mean age 57 years, mean RA duration 10 years), of whom 44 % were in remission by DAS28. Treatment was continued in 202 (59 %) patients, reduced in 57 (16 %), and intensified in 83 (24 %). In the 117 patients with active RA (DAS28 ≥ 3.2), treatment was intensified in 61 (52 %). Factors associated with treatment intensification were physician and patient VAS, and DAS28, but not the centre. In the multilevel regression analysis with intensification of treatment as dependent variable, the following factors were significantly associated: DAS28 [OR 3.67 (95 % CI 2.43-5.52)], patient VAS [OR 1.04 (95 % CI 1.01-1.08)], and have performed an ultrasound [OR 3.36 (95 % CI 1.47-7.68)]. Factors associated with time to the next scheduled visit (an average of 4.3 months) were patient and physician VAS, DAS28, and centre. In clinical practice, half of the patients with active RA maintain or reduce the treatment. The decision to intensify treatment in active RA as recommended by a treat-to-target strategy is complex in practice.

Results of a specific smoking cessation program for patients with arthritis in a rheumatology clinic.

The purpose of this study is to evaluate an intervention program in smoker patients. We selected consecutive active smoker patients with rheumatoid arthritis, spondyloarthritis, or connective tissue diseases. The intervention consisted of the following: (1) a baseline visit, which included verbal and written advice by the rheumatologist, emphasizing the practical benefits of smoking cessation. Patients completed a questionnaire that included smoking dependence tests and previous attempts to quit. (2) A follow-up visit to the nurse in the 3rd month for reinforcement and the receiving of pharmacological treatment to help patients quit smoking. The primary outcome was total abstinence in the last 7 days of a phone interview at 3, 6, and 12 months. The secondary outcome was a reduction in cigarette consumption by at least 50%. A total of 945 patients were screened. About 185 (19.5%) were current smokers, and 152 were included for intervention. In the previous 5 years, the mean annual withdrawal rate was 4.6%. The smoking cessation rate was 11.8, 14.4, and 15.7% at 3, 6, and 12 months (OR compared with previous cessation rate 3.8 (CI 95% 1.8-8.1)). Twenty-nine patients (19%) reduced ≥50% of the cigarette consumption at 12 months. The linear regression analysis showed that a score of less dependence (p = 0.03) and previous attempts to quit smoking (p = 0.04) were significantly associated with definitive smoking cessation at 12 months. One out of six patients quit smoking with the aid of an educational program which included verbal and written advice by the rheumatologist and the nurse. As far as we know, this is the first interventional study in smoker patients with arthritis.

Sex-specific impact of inflammation on traditional cardiovascular risk factors and atherosclerosis in axial spondyloarthritis. A multicentre study of 913 patients.

INTRODUCTION: The nature of the relationship between inflammation, cardiovascular (CV) risk factors and atherosclerosis in axial spondyloarthritis (axSpA) remains largely unknown and sex differences in this regard are yet to be assessed. METHODS: Study including 611 men and 302 women from the Spanish multicentre AtheSpAin cohort to assess CV disease in axSpA. Data on CV disease risk factors were collected both at disease diagnosis and at enrolment, and data on disease activity, functional indices and carotid ultrasonography only at enrolment. RESULTS: After a median disease duration of 9 years, patients of both sexes who at disease diagnosis had elevated acute phase reactants (APRs), more frequently had hypertension and obesity. The same occurred with dyslipidaemia in men and with diabetes mellitus in women. At enrolment, CV risk factors were independently associated with APR and with activity and functional indices, with various sex differences. C reactive protein (CRP) values were inversely associated with HDL-cholesterol in men (ß coefficient: -1.2 (95% CI: -0.3 to -0.07) mg/dL, p=0.001), while erythrocyte sedimentation rate values were positively associated with triglycerides in women (ß coefficient: 0.6 (95% CI: 0.04 to 1) mg/dL, p=0.035). Furthermore, only women showed an independent relationship between insulin resistance parameters and APR or disease activity. Both men and women with high-very high CV risk according to the Systematic Assessment of Coronary Risk Evaluation 2 and CRP levels higher than 3 mg/L at diagnosis of the disease presented carotid plaques significantly more frequently than those with normal CRP levels at disease diagnosis. CONCLUSION: Inflammation is associated with atherosclerosis and CV disease in axSpA. A gender-driven effect is observed in this relationship.

Outcome of an education and home-based exercise programme for patients with ankylosing spondylitis: a nationwide randomized study.

OBJECTIVES: This study aims to assess the impact of a structured education and home exercise programme in daily practice patients with ankylosing spondylitis. METHODS: A total of 756 patients with ankylosing spondylitis (72% males, mean age 45 years) participated in a 6-month prospective multicentre controlled study, 381 of whom were randomised to an education intervention (a 2-hour informative session about the disease and the implementation of a non-supervised physical activity programme at home) and 375 to standard care (controls). Main outcome measures included Bath Ankylosing Spondylitis Disease Activity and Functional Index (BASDAI, BASFI). Secondary outcome measures were 0-10 cm visual analog scale (VAS) for total pain, nocturnal pain and global disease activity and quality of life (ASQoL), knowledge of disease (self-evaluation ordinal scale) and daily exercise (diary card). RESULTS: At 6 months, the adjusted mean difference between control and educational groups for BASDAI was 0.32, 95% confidence interval (CI) 0.10-0.54, p=0.005, and for BASFI 0.31, 95%CI 0.12-0.51, p=0.002. Significant differences were found also in VAS for total pain, patient´s global assessment and in ASQoL. Patients in the education group increased their knowledge about the disease and its treatments significantly (p<0.001) and practised more regular exercise than controls (p<0.001). CONCLUSIONS: A structured education and home exercise programme for patients with ankylosing spondylitis in daily practice was feasible and helped to increase knowledge and exercise. Although statistically significant, the magnitudes of the clinical benefits in terms of disease activity and physical function were poor.

Scoring with the Berlin MRI method for assessment of spinal inflammatory activity in patients with ankylosing spondylitis: a calibration exercise among rheumatologists.

OBJECTIVES: To test the reliability of the Berlin MRI scoring method and the effect of a calibration exercise on the score's reliability among untrained readers in MRI examinations of patients with established ankylosing spondylitis (AS). METHODS: Eleven rheumatologists read blinded images of 20 AS patients before and after a two-day workshop on the Berlin MRI scoring method. Reliability (intra- and inter-reader) and concordance with the expert (all measured by intraclass correlation coefficient (ICC)) were compared before and after 2 weeks of the training. Feasibility in terms of time and difficulty was also measured. RESULTS: The mean Berlin score increased from (mean ± standard deviation) 5.04 ± 6.41 before to 6.40±7.08 after the calibration exercise (p<0.01). Inter-reader ICC decreased from 0.83 (95% CI: 0.75-0.93) to 0.78 (95% CI: 0.66-0.90), and intra-reader ICC from 0.89 (95% CI: 0.84-0.94) to 0.87 (95% CI: 0.82-0.92). Agreement with an experienced reader improved after the calibration exercise, with ICC = 0.59 (95% CI 0.45-0.76) before vs. ICC = 0.65 (95% CI 0.50-0.80) after training. CONCLUSIONS: The Berlin method is a reliable scoring method for assessment of spinal inflammatory activity by using MRI in patients with AS, even in the hands of inexperienced readers. A calibration exercise can improve feasibility and sensitivity of the scoring method.

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.

Effects of COVID-19 vaccination on disease activity in patients with rheumatoid arthritis and psoriatic arthritis on targeted therapy in the COVIDSER study.

OBJECTIVE: To investigate the influence of COVID-19 vaccination on disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients under targeted therapies. PATIENTS AND METHODS: 1765 vaccinated patients COVID-19, 1178 (66.7%) with RA and 587 (33.3%) with PsA from the COVID-19 registry in patients with rheumatic diseases (COVIDSER) project, were included. Demographics, disease characteristics, Disease Activity Score in 28 joints (DAS28) and targeted treatments were collected. DAS28-based flare rates and categorised disease activity distribution prevaccination and post vaccination were analysed by log-linear regression and contingency analyses, respectively. The influence of vaccination on DAS28 variation as a continuous measure was evaluated using a random coefficient model. RESULTS: The distribution of categorised disease activity and flare rates was not significantly modified by vaccination. Log-linear regression showed no significant changes in the rate of flares in the 6-month period after vaccination compared with the same period prior to vaccination in neither patients with RA nor patients with PsA. When DAS28 variations were analysed using random coefficient models, no significant variations in disease activity were detected after vaccination for both groups of patients. However, patients with RA treated with Janus kinase inhibitors (JAK-i) (1) and interleukin-6 inhibitor (IL-6-i) experienced a worsening of disease activity (1.436±0.531, p=0.007, and 1.201±0.550, p=0.029, respectively) in comparison with those treated with tumour necrosis factor inhibitor (TNF-i). Similarly, patients with PsA treated with interleukin-12/23 inhibitor (IL-12/23-i) showed a worsening of disease activity (4.476±1.906, p=0.019) compared with those treated with TNF-i. CONCLUSION: COVID-19 vaccination was not associated with increased rate of flares in patients with RA and PsA. However, a potential increase in disease activity in patients with RA treated with JAK-i and IL-6-i and in patients with PsA treated with IL-12/23-i warrants further investigation.

Sex differences in cardiovascular and disease-related features in axial spondyloarthritis. A multicenter study of 912 patients.

OBJECTIVES: To determine the potential impact of sex-specific disease-related characteristics on cardiovascular (CV) disease in axial spondyloarthritis (axSpA). METHODS: Cross-sectional study of the Spanish AtheSpAin cohort to study CV disease in axSpA. Data on carotid ultrasound and CV disease and disease-related features were collected. RESULTS: 611 men and 301 women were recruited. Classic CV risk factors were significantly less prevalent in women, who also showed a lower frequency of carotid plaques (p = 0.001), lower carotid intima-media thickness (IMT) values ​​(p<0.001) and CV events (p = 0.008). However, after adjustment for classic CV risk factors, only the differences with respect to carotid IMT remained statistically significant. Women showed higher ESR at diagnosis (p = 0.038), and more active disease (ASDAS, p = 0.012, and BASDAI, p<0.001). They had shorter disease duration (p<0.001), lower prevalence of psoriasis (p = 0.008), less structural damage (mSASSS, p<0.001), and less mobility limitation (BASMI, p = 0.033). To establish whether these findings could lead to sex differences in CV disease burden, we compared the prevalence of carotid plaques in men and women with the same level of CV risk stratified according to the Systematic Coronary Risk Evaluation (SCORE). Men included in the low-moderate CV risk SCORE category had more carotid plaques (p = 0.050), along with longer disease duration (p = 0.004), higher mSASSS (p = 0.001) and psoriasis (p = 0.023). In contrast, in the high-very high-risk SCORE category, carotid plaques were observed more frequently in women (p = 0.028), who were characterized as having worse BASFI (p = 0.011), BASDAI (p<0.001) and ASDAS (p = 0.027). CONCLUSION: Disease-related features may influence the expression of atherosclerosis in patients with axSpA. This may be especially applicable to women at high CV risk, characterized by greater disease severity and more severe subclinical atherosclerosis than men, suggesting a stronger interaction between disease activity and atherosclerosis in women with axSpA.

Change in the discontinuation pattern of tumour necrosis factor antagonists in rheumatoid arthritis over 10 years: data from the Spanish registry BIOBADASER 2.0.

OBJECTIVE: To investigate in rheumatoid arthritis (RA) the rate and reason of discontinuation of tumour necrosis factor (TNF) antagonists over the past decade. METHODS: RA patients in BIOBADASER 2.0 were stratified according to the start date of their first TNF antagonist into 2000-3, 2004-6 and 2007-9 interval years. Cumulative incidence function of discontinuation for inefficacy or toxicity was estimated with the alternative reason as competing risk. Competing risks regression models were used to measure the association of study groups with covariates and reasons for discontinuation. Association is expressed as subhazard ratios (SHR). RESULTS: 2907 RA patients were included in the study. Competing risk regression for inefficacy shows larger SHR for patients starting treatment in 2004-6 (SHR 2.57; 95% CI 1.55 to 4.25) and 2007-9 (SHR 3.4; 95% CI 2.08 to 5.55) than for those starting in 2000-3, after adjusting for TNF antagonists, clinical activity and concomitant treatment. Competing risk regression analysis for adverse events revealed no differences across the three time intervals. CONCLUSIONS: In RA, the discontinuation rate of TNF antagonists in the first year of treatment is higher more recently than a decade ago, inefficacy being the main reason for the increased rate. The rate of discontinuation for adverse events has remained stable.

Implications of FRAX® adjusted for recent fracture on the indication of treatment in an FLS.

We analyzed the practical consequences of applying an adjusted FRAX® for recent fractures in a FLS. After analyzing 2777 patients, we concluded that the adjusted FRAX® is irrelevant when calculating FRAX® with DXA and is only useful for fractures of the humerus when DXA is not available. PURPOSE: A FRAX® adjusted to fractures less than 2 years old has been proposed. The objective of this work was to analyze the clinical implications of applying the adjusted FRAX® instead of the classic FRAX® in a fracture liaison service (FLS) unit. METHODS: Adults aged 50 years or older with fragility fractures (hip, spine, humerus, and forearm) that occurred in the 12 months prior to the baseline visit were included. We recorded demographic data, type of fracture, DXA, classic FRAX®, and FRAX® adjusted for recent fractures and indications for anti-osteoporotic medication (AOM) following the guidelines of the Spanish Society of Rheumatology. RESULTS: A total of 2777 patients were included, mean age 73 years, 84% women. The type of fracture was as follows: forearm (n = 958; 34.5%), hip (n = 781; 28.1%), humerus (n = 642; 23.1%), and spine (n = 397, 14.3%). DXA was performed in 2134 cases (76.8%). A total of 2522 patients (90.8%) were candidates for AOM (100% involving the hip and spine, 83% forearm, and 85% humerus). FRAX®-hip ≥ 3% increased from 1601 to 1775 cases (57.6 to 64%). The average FRAX®-hip (SD) increased from 5.7 (6) to 7.5 (9) (4.6 to 8.8 in males and 5.9 to 7.3 in females). The percentage of forearm fracture candidates for AOM, with or without DXA, did not change after FRAX®-hip adjustment, while the number of patients with humerus fractures increased from 59 to 80% in those who did not have DXA. In the entire sample, FRAX®-adjusted led to an indication of AOM for 15 additional patients (0.5% of major fractures): 14 with a humerus fracture and 1 with a forearm fracture. CONCLUSIONS: The adjusted FRAX® for recent fractures in an FLS unit in an adjusted FRAX® is irrelevant when calculating FRAX® with DXA; in fact, it is only useful for fractures of the humerus when DXA is not available.

Long-term persistence of treatment after hip fracture in a fracture liaison service.

Long-term adherence to antiosteoporosis medication (AOM) in the setting of a fracture liaison service (FLS) are not well known. Patients ≥ 50 with hip fracture seen in an FLS and recommended for treatment to prevent new fractures were analyzed. Baseline data included demographics, identification mode, previous treatment and FRAX items. Patient records were reviewed 3-8 years later, and these data were collected: (1) survival; (2) major refracture; (3) initiation of treatment, proportion of days covered (PDC) and persistence with AOM. 372 patients (mean age, 79 years; 76% women) were included. Mean follow-up was 47 months, 52 patients (14%) had a refracture (22 hip) and 129 (34.5%) died. AOM was started in 283 patients (76.0%). Factors associated with initiation of AOM were previous use of bisphosphonate (OR 9.94; 95% CI 1.29-76.32) and a lower T-score lumbar (OR 0.80; 95% CI 0.65-0.99). Persistence decreased to 72.6%, 60% and 47% at 12, 36 and 60 months. A PDC > 80% was confirmed in 208 patients (55.7%) and associated with previous use of bisphosphonate (OR 3.38; 95% CI 1.34-8.53), treatment with denosumab (OR 2.69; 95% CI:1.37-5.27), and inpatient identification (OR 2.26; 95% CI 1.18-4.34). Long-term persistence with AOM was optimal in patients with hip fracture seen at an FLS. A PDC > 80% was associated with inpatient identification and prescription of denosumab.

Real-World Effectiveness and Treatment Retention of Secukinumab in Patients with Psoriatic Arthritis and Axial Spondyloarthritis: A Descriptive Observational Analysis of the Spanish BIOBADASER Registry.

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.