A high prevalence of periodontitis has been reported in rheumatoid arthritis (RA) patients, although the strength of this association, its temporal link and the possible relationship between the ...severity of periodontitis and RA disease activity remain unclear. The objective of this work was to investigate whether periodontitis is associated with RA and whether periodontitis severity is linked to RA disease activity.
This case-control study included 187 patients diagnosed with RA and 157 control patients without inflammatory joint disease. RA disease activity and severity were evaluated by the Disease Activity Score 28, the Simplified Disease Activity Index, the Clinical Disease Activity Index, rheumatoid factor, anti-citrullinated protein antibody titers, the erythrocyte sedimentation rate, C-reactive protein, presence of extra-articular manifestations and type of RA therapy. Exposure severity was assessed by the following periodontal parameters: plaque index, bleeding on probing, probing pocket depth and clinical attachment levels. Sociodemographic variables and comorbidities were evaluated as confounding variables. Outcome and exposure variables were compared by both parametric and nonparametric tests, and possible associations were assessed through regression analysis with a calculation for the adjusted odds ratio (OR).
A significant association was demonstrated between periodontitis and RA with an adjusted OR of 20.57 (95% CI 6.02-70.27, p < 0.001). Compared with controls, all parameters related to periodontal status (plaque index, bleeding on probing, probing pocket depth and clinical attachment levels) were significantly worse in RA patients (p < 0.001). Periodontitis severity was significantly associated with RA disease activity (p < 0.001), showing in an ordinal logistic regression model an association between periodontal severity and disease activity with an adjusted OR of 2.66 (95% CI 1.24-5.74, p = 0.012).
A significant association was demonstrated between periodontitis and RA, independent of other confounders. This association was more evident in patients with pronounced periodontal disease and higher RA disease activity.
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.
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.
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).
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.
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.
(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.
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.
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).
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.
Patients with rheumatoid arthritis (RA) have an increased risk of infection and malignancy compared with the general population. Infection risk is increased further with the use of disease-modifying ...antirheumatic drugs (DMARDs), whereas evidence on whether the use of biologic DMARDs increases cancer risk remains equivocal. This single-arm, post-marketing study estimated the incidence of prespecified infection and malignancy outcomes in patients with RA treated with intravenous or subcutaneous abatacept.
Data were included from seven European RA quality registries: ATTRA (Anti-TNF Therapy in Rheumatoid Arthritis Czech Republic), DANBIO (Danish Rheumatologic Database), ROB-FIN (National Registry of Antirheumatic and Biological Treatment in Finland), ORA (Orencia and Rheumatoid Arthritis France), GISEA (Italian Group for the Study of Early Arthritis), BIOBADASER (Spanish Register of Adverse Events of Biological Therapies in Rheumatic Diseases), and the SCQM (Swiss Clinical Quality Management) system. Each registry is unique with respect to design, data collection, definition of the study cohort, reporting, and validation of outcomes. In general, registries defined the index date as the first day of abatacept treatment and reported data for infections requiring hospitalization and overall malignancies; data for other infection and malignancy outcomes were not available for every cohort. Abatacept exposure was measured in patient-years (p-y). Incidence rates (IRs) were calculated as the number of events per 1000 p-y of follow-up with 95% confidence intervals.
Over 5000 patients with RA treated with abatacept were included. Most patients (78-85%) were female, and the mean age range was 52-58 years. Baseline characteristics were largely consistent across registries. Among patients treated with abatacept, IRs for infections requiring hospitalization across the registries ranged from 4 to 100 events per 1000 p-y, while IRs for overall malignancy ranged from 3 to 19 per 1000 p-y.
Despite heterogeneity between registries in terms of design, data collection, and ascertainment of safety outcomes, as well as the possibility of under-reporting of adverse events in observational studies, the safety profile of abatacept reported here was largely consistent with previous findings in patients with RA treated with abatacept, with no new or increased risks of infection or malignancy.
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.
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.
Retrospective non-interventional database analysis.
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.
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).
With this novel approach, the factors associated with long-term retention were identified in the initial period of rapid discontinuation of golimumab.
The purpose of this study was to assess the prevalence, associated factors, and impact on mortality of primary respiratory disease in a large systemic lupus erythematosus (SLE) retrospective cohort.
...All adult patients in the RELESSER-TRANS (Registry of Systemic Lupus Erythematosus Patients of the Spanish Society of Rheumatology SER, cross-sectional phase) registry were retrospectively investigated for the presence of primary pleuropulmonary manifestations.
In total 3215 patients were included. At least one pleuropulmonary manifestation was present in 31% of patients. The most common manifestation was pleural disease (21%), followed by lupus pneumonitis (3.6%), pulmonary thromboembolism (2.9%), primary pulmonary hypertension (2.4%), diffuse interstitial lung disease (2%), alveolar hemorrhage (0.8%), and shrinking lung syndrome (0.8%). In the multivariable analysis, the variables associated with the development of pleuropulmonary manifestation were older age at disease onset (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.02-1.04), higher SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) scores (OR 1.03, 95% CI 1.00-1.07), the presence of Raynaud's phenomenon (OR 1.41, 95% CI 1.09-1.84), secondary antiphospholipid syndrome (OR 2.20, 95% CI 1.63-2.97), and the previous or concomitant occurrence of severe lupus nephritis, (OR 1.48, 95% CI 1.12-1.95) neuropsychiatric manifestations (OR 1.49, 95% CI 1.11-2.02), non-ischemic cardiac disease (OR 2.91, 95% CI 1.90-4.15), vasculitis (OR 1.81, 95% CI 1.25-2.62), hematological manifestations (OR 1.31, 95% CI 1.00-1.71), and gastrointestinal manifestations, excluding hepatitis (OR 2.05, 95% CI 1.14-3.66). Anti-RNP positivity had a clear tendency to significance (OR 1.32, 95% CI 1.00-1.75; P = 0.054). The development of pleuropulmonary manifestations independently contributes to a diminished survival (hazard ratio of 3.13). However, not all complications will influence the prognosis in the same way. Whereas the occurrence of pleural disease or pulmonary thromboembolism has a minimal impact on the survival of these patients, the remaining manifestations have a major impact on mortality.
Except for pleural disease, the remaining respiratory manifestations are very uncommon in SLE (<4%). Pleuropulmonary manifestations independently contributed to a decreased survival in these patients.
The better understanding of the safety of biologic DMARDs (bDMARDs), as well as the emergence of new bDMARDs against different therapeutic targets and biosimilars have likely influenced the use ...patterns of these compounds over time. The aim of this study is to assess changes in demographic characteristics, disease activity and treatment patterns in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) who started a first- or second-line biologic between 2007 and mid-2020. Patients diagnosed with RA, PsA or AS included in the BIOBADASER registry from January 2007 to July 2020 were included. According to the start date of a first- or second-line biologic therapy, patients were stratified into four time periods: 2007-2009; 2010-2013; 2014-2017; 2018-2020 and analyzed cross-sectionally in each period. Demographic and clinical variables, as well as the type of biologic used, were assessed. Generalized linear models were applied to study the evolution of the variables of interest over time periods, the diagnosis, and the interactions between them. A total of 4543 patients initiated a first biologic during the entire time frame of the study. Over the four time periods, disease evolution at the time of biologic initiation (p < 0.001), disease activity (p < 0.001), retention rate (p < 0.001) and the use of tumor necrosis factor inhibitors as a first-line treatment (p < 0.001) showed a significant tendency to decrease. Conversely, comorbidities, as assessed by the Charlson index (p < 0.001), and the percentage of patients using bDMARDs in monotherapy (p < 0.001), and corticosteroids (p < 0.001) tended to increase over time. Over the entire period of the study's analysis, 3289 patients started a second biologic. The following trends were observed: decreased DAS28 at switching (p < 0.001), lower retention rates (p = 0.004), and incremental changes to the therapeutic target between the first and second biologic (p < 0.001). From 2007 until now rheumatic patients who started a biologic were older, exhibited less clinical activity, presented more comorbidities, and switched to a different biologic more frequently and earlier.
To assess whether age, at the beginning of biologic treatment, is associated with the time a first adverse event (AE) appears in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), ...or psoriatic arthritis (PsA).
All patients in the BIOBADASER registry diagnosed with RA, AS, and PsA, and classified as young (< 25 years old), adult (25-64 years old), elderly (65-75 years old) or very elderly (> 75 years old) at start of biological treatment were included. Factors associated with the appearance of a first AE using adjusted incidence rate ratios (IRR) (Poisson regression) were analyzed. Survival to first AE was studied by Kaplan-Meier analysis and hazard ratios (HR) by Cox regression.
2483 patients were included: 1126 RA, 680 PsA, and 677 AS. Age group stratification was as follows: 63 young, 2127 adults, 237 elderly, and 56 very elderly. Regression model revealed an increased probability of suffering a first AE at age 65 years or older IRR elderly: 1.42 (CI95% 1.13-1.77). Other characteristics associated with AE were female gender, the use of DMARDs, including methotrexate, the presence of comorbidities, and the time of disease duration. Factors that had the greatest impact on survival over a first AE were age > 75 years HR 1.50 (1.01-2.24) and female gender HR 1.42 (1.22-1.64).
Age at the start of treatment and female gender are key factors associated with the appearance of a first AE with biologics. Other factors related to patient status and treatment were also associated with a first AE in rheumatic patients treated with biologics.
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.
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.
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.
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.
Aim
To assess the golimumab retention rate during up to 8 years of follow up, and any associated factors.
Methods
Retrospective analysis of the BIOBADASER (Spanish registry of biological drugs) ...database, assessing all adults who had ever started golimumab >6 months before the analysis for an approved indication (rheumatoid arthritis RA, axial spondyloarthritis SpA or psoriatic arthritis PsA).
Results
Among 885 patients (RA 267, axial SpA 370, PsA 248) receiving 944 cycles of golimumab, the retention rate of golimumab was 71.1% (95% confidence interval: 68.0–73.9) at year 1% and 37.7% (95% CI: 33.3–42.1) at year 7 and at year 8. Retention was higher when golimumab was used as the first biological drug (81.7% at year 1, 49.9% at year 7, p < 0.001). In Cox regression analysis, factors associated with golimumab retention included use as first‐line therapy (hazard ratio HR for discontinuation 1.52 for second‐ and 1.79 for third/later‐line vs. first‐line), use in axial SpA or PsA rather than RA (HR for axial SpA vs. RA 0.59, for PsA vs. Rheumatoid arthritis 0.67), and treatment with concomitant methotrexate (HR 0.67). Factors associated with golimumab discontinuation were corticosteroid use (HR 1.46) and disease activity above median (HR 1.29) at golimumab initiation.
Conclusion
Based on this retrospective analysis of the BIOBADASER registry, nearly two‐fifths (37.7%) of adult rheumatology patients initiating golimumab will remain on treatment for 8 years, with a higher probability of retention in axial SpA or PsA indications and when golimumab is used as first biologic.
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