Biological therapies have improved the clinical course and quality of life of rheumatoid arthritis (RA) patients. Despite the availability and effectiveness of these treatments, some patients ...experience multiple failures to biologic disease-modifying antirheumatic drugs (bDMARDs), constituting a particular challenge to clinicians.
This study aims to determine the percentage of rheumatoid arthritis (RA) patients who fail to respond to subsequent bDMARDs, describe their characteristics, and identify specific baseline and early features during the first bDMARD as possible predictors of consecutive multiple bDMARD failure.
This is a longitudinal study involving RA patients from the prospective biological cohort drawn from the La Paz University Hospital RA Registry (RA-Paz), starting a bDMARD during the years 2000 to 2019. Patients who presented insufficient response (due to primary or secondary inefficacy) to at least three bDMARDs or two bDMARDs with different mechanism of action were considered multi-refractory (MR-patients). Patients who achieved low disease activity or remission (by DAS-28) with the first bDMARD and maintained this over a follow-up period of at least 5 years were considered non-refractory (NR-patients).
A total of 41 out of 402 (10%) patients were MR-patients and 71 (18%) NR-patients. In the multivariate analysis, the presence of erosions, younger age, higher baseline DAS-28 and mostly achieving delta-DAS < 1.2 after 6 months of the first bDMARD (OR 11.12; 95% CI 3.34-26.82) were independently associated with being MR-patients to bDMARDs.
In our cohort, 10% of patients with RA were observed to have multi-refractoriness to bDMARDs. This study supports the contention that younger patients with erosive disease and especially the early absence of clinical response to the first bDMARDs are predictors of multi-refractoriness to consecutive biologics. Hence, patients with these characteristics should be monitored more closely and may benefit from personalized treatments.
Abstract
To analyze the epidemiology, clinical features and costs of hospitalized patients with gout during the last decade in Spain. Retrospective observational study based on data from the Minimum ...Basic Data Set (MBDS) from the Spanish National Health Service database. Patients ≥ 18 years with any gout diagnosis at discharge who had been admitted to public or private hospitals between 2005 and 2015 were included. Patients were divided in two periods: p1 (2005–2010) and p2 (2011–2015) to compare the number of hospitalizations, mean costs and mortality rates. Data from 192,037 patients with gout was analyzed. There was an increase in the number of hospitalized patients with gout (p < 0.001). The more frequent comorbidities were diabetes (27.6% of patients), kidney disease (26.6%) and heart failure (19.3%). Liver disease (OR 2.61), dementia (OR 2.13), cerebrovascular diseases (OR 1.57), heart failure (OR 1.41), and kidney disease (OR 1.34) were associated with a higher mortality risk. Women had a lower risk of mortality than men (OR 0.85). General mortality rates in these hospitalized patients progressively increased over the years (p < 0.001). In addition, costs gradually rose, presenting a significant increase in p2 even after adjusting for inflation (p = 0.001). A progressive increase in hospitalizations, mortality rates and cost in hospitalized patients with gout was observed. This harmful trend in a preventable illness highlights the need for change and the search for new healthcare strategies.
The presence of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) autoantibodies contributes to the current rheumatoid arthritis (RA) classification criteria. These criteria ...involve stratification on antibody levels, which limits reproducibility, and underperform in the RA patients without RF and anti-CCP. Here, we have explored if two anti-acetylated peptide antibodies (AAPA), anti-acetylated lysine (AcLys) and anti-acetylated ornithine (AcOrn), could improve the performance of the current criteria. The analysis was done in 1062 prospectively-followed early arthritis (EA) patients. The anti-AcOrn were more informative than the anti-AcLys, the conventional RA antibodies and the anti-carbamylated protein antibodies. The anti-AcOrn produced a classification that did not require antibody levels and showed improved specificity (77.6% vs. 72.6%, p = 0.003) and accuracy (79.0% vs. 75.8%, p = 0.002) over the current criteria. These improvements were obtained with a scoring system that values concordance between anti-AcOrn, RF and anti-CCP. No significant gain was obtained in sensitivity (80.2% vs. 78.8%, p = 0.25) or in improving the classification of the RA patients lacking RF and anti-CCP, although the anti-AcOrn ranked first among the analysed new antibodies. Therefore, the anti-AcOrn antibodies could contribute to the improvement of RA classification criteria by exploiting antibody concordance.
Aims:
First, to compare clinical features and biological disease modifying anti-rheumatic drugs (bDMARDs) response in patients with axial spondyloarthritis (axSpA) and axial psoriatic arthritis ...(axPsA). Second, to identify possible predictors of treatment response in both entities.
Methods:
One-year follow-up, observational, single-center study including all patients with axSpA or axPsA who started bDMARDs therapy. Clinical features were collected at baseline while disease activity was measured at baseline, 6 and 12 months by the Ankylosing Spondylitis Disease Activity Score and the Physician Global Assessment. The frequency of patients achieving inactive disease (ID), low disease activity (LDA), high or very high disease activity and clinical improvement were compared between axSpA and axPsA. Baseline predictor factors for achieving treatment response were identified through regression models, using odds ratio (OR) as an estimate.
Results:
In total, 352 patients were included: 287 (81.5%) axSpA and 65 (18.5%) axPsA. No significant differences at baseline were observed between the two diseases for most of the characteristics. While HLA-B27 positivity was associated with axSpA (OR = 5.4; p < 0.001), peripheral manifestations were associated with axPsA (OR = 4.7; p < 0.001). The frequency of patients with axSpA and axPsA achieving ID/LDA after 6 and 12 months of bDMARDs was comparable: 53% versus 58%, p = 0.5; and 58% versus 60%, p = 0.9, respectively. Both diseases also presented similar clinical improvement. In axSpA and axPsA, male gender seemed to be associated with achieving LDA OR at 12 months visit = 2.8 (p < 0.01) and 2.7 (p = 0.09).
Conclusion:
In clinical practice, patients with axSpA and axPsA present numerous similarities, including comparable medium-term clinical response to bDMARDs. Male gender could be a predictor of treatment response in both diseases.Keyword: axial spondyloarthritis, psoriatic arthritis, axial involvement, clinical characteristics
Background:
Despite advances in the treatment of rheumatoid arthritis (RA) and the wide range of therapies available, there is a percentage of patients whose treatment presents a challenge for ...clinicians due to lack of response to multiple biologic and target-specific disease-modifying antirheumatic drugs (b/tsDMARDs).
Objective:
To develop and validate an algorithm to predict multiple failure to biological therapy in patients with RA.
Design:
Observational retrospective study involving subjects from a cohort of patients with RA receiving b/tsDMARDs.
Methods:
Based on the number of prior failures to b/tsDMARDs, patients were classified as either multi-refractory (MR) or non-refractory (NR). Patient characteristics were considered in the statistical analysis to design the predictive model, selecting those variables with a predictive capability. A decision algorithm known as ‘classification and regression tree’ (CART) was developed to create a prediction model of multi-drug resistance. Performance of the prediction algorithm was evaluated in an external independent cohort using area under the curve (AUC).
Results:
A total of 136 patients were included: 51 MR and 85 NR. The CART model was able to predict multiple failures to b/tsDMARDs using disease activity score-28 (DAS-28) values at 6 months after the start time of the initial b/tsDMARD, as well as DAS-28 improvement in the first 6 months and baseline DAS-28. The CART model showed a capability to correctly classify 94.1% NR and 87.5% MR patients with a sensitivity = 0.88, a specificity = 0.94, and an AUC = 0.89 (95% CI: 0.74–1.00). In the external validation cohort, 35 MR and 47 NR patients were included. The AUC value for the CART model in this cohort was 0.82 (95% CI: 0.73–0.9).
Conclusion:
Our model correctly classified NR and MR patients based on simple measurements available in routine clinical practice, which provides the possibility to characterize and individualize patient treatments during early stages.
ObjectivesThe European Alliance of Associations for Rheumatology (EULAR) recommendations for the use of imaging in large vessel vasculitis establish that an imaging test supported by clinical pretest ...probability (PTP) is sufficient for the diagnosis of giant cell arteritis (GCA). Our objective was to determine the validity of the EULAR recommendations on the use of Colour duplex ultrasound (CDUS) in GCA after calculating the PTP.MethodsWe collected data of all patients referred to our fast-track clinic between 2016 and 2020. The Southend pretest probability score (SPTPS) was calculated and classified as low (LR), intermediate and high risk (HR) according to the values obtained by its authors, <9, 9–12 and >12, respectively. All patients underwent a CDUS of the temporal arteries with their common, parietal and frontal branches, and the most also axillary (86.5%), and subclavian and carotid arteries. The gold-standard diagnosis was made according to the physician’s criteria after at least 9 months of follow-up.ResultsOf the 297 referred patients, 97 (32.7%) were diagnosed with GCA. The SPTPS area under the ROC curve was 0.787. The LR category included 105 patients (35.4%), of which 10 (9.5%) had GCA and 1 had a CDUS false negative result. The HR category included 67 patients (22.5%), 47 with GCA, and in 1 case the CDUS result was a false positive.ConclusionCombining the results of a PTP score, such as SPTPS, and the CDUS allows for an accurate diagnosis of GCA, as established by the EULAR group, with less than 2% misclassification of diagnosis.
ObjectivesTo determine the frequency of sustained remission (R) or low diseas activity (LDA) in patients with axial spondyloarthritis (axSpA) undergoing long-term biological therapy and to analyse ...predictive factors for achieving these outcomes.DesignProspective, observational cohort study.SettingSpanish hospital.ParticipantsPatients with axSpA who initiated biological treatment between 2003 and 2017.InterventionAssessment of demographic and clinical characteristics at the beginning of treatment and disease activity every 6 months up to a maximum of 2 years.Main outcome measuresDisease activity was measured by Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index and C reactive protein (BASDAI&CRP). Sustained R was defined as ASDAS<1.3 and/or BASDAI <2 and normal CRP while sustained LDA was defined as ASDAS <2.1 and/or BASDAI <4 and normal CRP on at least three consecutive visits.ResultsIn total 186 patients (66.1% men and 75.3% with radiographic sacroiliitis) were included. Overall, 76.8% of patients achieved ASDAS R/LDA (R53.2%/LDA23.6%) in at least one visit. Forty per cent (R17.6%/LDA22.4%) of the patients fulfilled the sustained ASDAS R/LDA state, whereas only 30.8% maintained this status (R14.8%/LDA15.9%) according to BASDAI&CRP. In the multivariate analysis, male sex (OR=4.01), younger age at the beginning of biological therapy (OR=0.96) and an HLA*B27 positive status (OR=4.30) were associated with achieving sustained ASDAS R/LDA.ConclusionsIn clinical practice, around one-third of patients on biological disease-modifying antirheumatic drugs achieve a sustained R/LDA status, but these rates drop to less than one in five when targeting remission, preventing the use of the latter as a feasible target. Male sex, HLA*B27 positivity and younger age at the beginning of biological therapy are the main predictors for achieving sustained R/LDA.
Vaspin is a novel anti-inflammatory adipokine associated with cardiovascular (CV) disease and inflammation in chronic inflammatory conditions different from axial spondyloarthritis (axSpA). Given the ...high incidence of CV disease (mainly due to accelerated atherosclerosis) exhibited by axSpA patients, we wondered if vaspin could also be a key molecule in this process. However, data on the role of vaspin regarding atherosclerotic disease in the context of axSpA is scarce. For this reason, we aimed to evaluate the implication of vaspin, at the genetic and serological level, in subclinical atherosclerosis and CV risk in axSpA.
This study included 510 patients diagnosed with axSpA. Carotid ultrasound (US) was performed to evaluate the presence of subclinical atherosclerosis. Three vaspin gene variants (rs2236242, rs7159023, and rs35262691) were genotyped by TaqMan probes. Serum vaspin levels were assessed by enzyme-linked immunosorbent assay. Statistical analysis was performed using STATA® v.11.1.
Serum vaspin levels were significantly higher in female patients than in males and also in obese patients when compared to those with normal weight (p < 0.05). At the genetic level, we disclosed that the minor allele of rs2236242 (A) was associated with lower serum vaspin levels in axSpA, while the rs7159023 minor allele (A) was linked to higher serum levels (p < 0.05). When the three polymorphisms assessed were combined conforming haplotypes, we disclosed that the TGC haplotype related to high serum levels of vaspin (p = 0.01). However, no statistically significant association was observed between vaspin and markers of subclinical atherosclerosis, both at the genetic and serological level.
Our results revealed that vaspin is linked to CV risk factors that may influence on the atherosclerotic process in axSpA. Additionally, we disclosed that serum vaspin concentration is genetically modulated in a large cohort of patients with axSpA.
Classification of patients with rheumatoid arthritis (RA) as quickly as possible improves their prognosis. This reason motivates specially dedicated early arthritis (EA) clinics. Here, we have used ...1062 EA patients with two years of follow-up to explore the value of anti-carbamylated protein (anti-CarP) antibodies, a new type of RA specific autoantibodies, for classification. Specifically, we aimed to determine whether the addition of anti-CarP antibodies to IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies, which are helpful in RA classification, improves it or not. Our analysis showed that incorporation of the anti-CarP antibodies to combinations of the other two antibodies (all joint by the OR Boolean operator) produces a modest increase in sensitivity (2.2% higher), at the cost of decreased specificity (8.1% lower). The cost-benefit ratio was more favorable in the patients lacking the other autoantibodies. However, it did not improve by considering different titer levels of the anti-CarP antibodies, or after exhaustively exploring other antibody combinations. Therefore, the place in RA classification of these antibodies is questionable in the context of current treatments and biomarkers. This conclusion does not exclude their potential value for stratifying patients in joint damage, disease activity, disability, or mortality categories.
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