Do Radiographic Joint Damage and Disease Activity Influence Functional Disability Through Different Mechanisms? Direct and Indirect Effects of Disease Activity in Established Rheumatoid Arthritis

2013 ◽  
Vol 40 (9) ◽  
pp. 1505-1512 ◽  
Author(s):  
Sandhya C. Nair ◽  
Johannes W.J. Bijlsma ◽  
Jacobien H. van der Werf ◽  
Maaike J. van der Veen ◽  
Suzanne P. Linn-Rasker ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Functional Disability ◽  
Functional Decline ◽  
Joint Damage ◽  
Treatment Strategies ◽  
Joint Disease ◽  
Influence Functional ◽  
Over Time ◽  
Predictive Effect

Objective.To explore the relationship between rheumatoid arthritis (RA) disease activity and functional disability over time, considering indirect (predictive) and direct (concurrent) associations as well as the influence of radiographic joint damage and treatment strategy.Methods.Functional disability [Health Assessment Questionnaire (HAQ)], disease activity [28-joint Disease Activity Score (DAS28)], and radiographic joint damage [Sharp/van der Heijde score (SHS)] were measured in 4 consecutive randomized controlled trials with increasingly intensive (tight control) treatment strategies. Average followup time for the 3 cohorts was 97, 53, and 50 months, respectively. Next to current DAS28, the previous DAS28 was used to study the predictive effect of a change in DAS28 on progression of functional disability (HAQ). Finally, it was investigated whether SHS mediated the predictive effect of DAS28.Results.In patients treated with intensive treatment strategies, the progression of HAQ over time was statistically significantly less (p < 0.0001). The predictive influence of DAS28 on HAQ progression increased over the duration of the disease. SHS was not found to influence HAQ progression and did not mediate the predictive effect of DAS28. In the less intensively treated patients, the direct effect of disease activity decreased with disease duration, and contrarily, SHS did influence HAQ progression, but was not found to (fully) mediate the predictive effect of DAS28.Conclusion.In patients with RA treated with modern treatment strategies, there is less functional decline over time. Further, disease activity does predict functional decline but joint damage does not. This might indicate that factors associated with cumulative disease activity but not visible on radiographs can influence functional decline in patients with RA. This further underlines the importance of disease activity as a treatment target in early RA and in established RA.

scholarly journals Has the Severity of Rheumatoid Arthritis at Presentation Diminished Over Time?

2014 ◽  
Vol 41 (8) ◽  
pp. 1590-1599 ◽  
Author(s):  
Janet G. Diffin ◽  
Mark Lunt ◽  
Tarnya Marshall ◽  
Jacqueline R. Chipping ◽  
Deborah P.M. Symmons ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Drug Exposure ◽  
Functional Disability ◽  
Health Assessment ◽  
Joint Disease ◽  
Symptom Duration ◽  
Recent Onset ◽  
American College Of Rheumatology ◽  
Over Time

Objective.To examine the pattern of disease severity in patients with rheumatoid arthritis (RA) at presentation to the Norfolk Arthritis Register (NOAR) over 20 years.Methods.NOAR is a primary-care–based cohort of patients with recent-onset inflammatory polyarthritis. At baseline, subjects are assessed and examined by a research nurse. The Health Assessment Questionnaire (HAQ) is administered and the DAS28 (28-joint Disease Activity Score) is calculated. Information is collected on disease-modifying antirheumatic drug exposure. In this study, patients (symptom duration of < 2 years at baseline) were grouped into 4 cohorts (Cohort 1: 1990–1994; Cohort 2: 1995–1999; Cohort 3: 2000–2004; Cohort 4: 2005–2008). The American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria for RA were applied retrospectively at baseline. Regression analyses were used to examine whether calendar year of presentation to NOAR was associated with baseline HAQ and DAS28 scores. Potential confounders included age at symptom onset, sex, rheumatoid factor, and anticyclic citrullinated peptide antibody positivity.Results.A total of 1724 patients met the ACR/EULAR 2010 RA criteria at baseline. Unadjusted mean DAS28 scores decreased over time. Calendar year of presentation to NOAR was significantly associated with lower DAS28 scores over time [Y = 4.51 + (–0.56 × year) + (0.44 × year2)]. Although unadjusted median HAQ scores increased over time, calendar year of presentation to NOAR was not significantly associated with HAQ scores [Y = (1.1) + (0.023 × year) + (0.05 × year2)]. Similar results were observed in each subpopulation of patients.Conclusion.While baseline disease activity has lessened slightly over time, there has been no improvement in baseline levels of functional disability.

scholarly journals Abatacept Plus Methotrexate Provides Incremental Clinical Benefits Versus Methotrexate Alone in Methotrexate-naive Patients with Early Rheumatoid Arthritis Who Achieve Radiographic Nonprogression

2011 ◽  
Vol 38 (11) ◽  
pp. 2362-2368 ◽  
Author(s):  
ALVIN F. WELLS ◽  
RENE WESTHOVENS ◽  
DIANE MONIZ REED ◽  
LUCIANA FANTI ◽  
JEAN-CLAUDE BECKER ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Clinical Outcomes ◽  
Disease Activity Score ◽  
Health Assessment ◽  
Joint Damage ◽  
Joint Disease ◽  
Activity Score ◽  
Double Blind ◽  
American College Of Rheumatology

Objective.This article reports 1-year clinical outcomes in the subgroup of patients with rheumatoid arthritis in the Abatacept study to Gauge Remission and joint damage progression in methotrexate-naive patients with Early Erosive rheumatoid arthritis (AGREE) who achieved radiographic nonprogression at the end of the double-blind phase.Methods.Patients who achieved radiographic nonprogression (change from baseline in total Sharp score ≤ 0 at 12 months) with abatacept plus methotrexate (MTX) or MTX alone were eligible for this analysis. Clinical outcomes were remission, defined by 28-joint Disease Activity Score (DAS28) using C-reactive protein (CRP), low Disease Activity Score (LDAS), American College of Rheumatology (ACR) scores, physical function (Health Assessment Questionnaire), and tender and swollen joint counts. Safety was assessed at each visit.Results.Patients in the abatacept plus MTX and MTX monotherapy groups had similar baseline characteristics and were similar to the overall study population. The proportion of patients who achieved DAS28 (CRP) remission or LDAS was greater with abatacept plus MTX vs MTX alone [43.2% vs 22.7% (p < 0.001) and 57.4% vs 40.6% (p = 0.008), respectively]. More patients receiving abatacept plus MTX achieved key ACR responses, including major clinical response (27.3% vs 11.9%; p < 0.001). Safety profiles were similar in both treatment groups.Conclusion.More MTX-naive patients with early RA who achieved radiographic nonprogression taking abatacept plus MTX also achieved DAS28 (CRP)-defined remission and LDAS compared with patients who received MTX alone, supporting the use of abatacept as a first-line biologic in combination with disease-modifying antirheumatic drugs.

scholarly journals Is Tightly Controlled Disease Activity Possible with Online Patient-reported Outcomes?

2014 ◽  
Vol 41 (4) ◽  
pp. 640-647 ◽  
Author(s):  
Margot J. Walter ◽  
S.H. Mohd Din ◽  
Johanna M. Hazes ◽  
E. Lesaffre ◽  
P.J. Barendregt ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Patient Reported Outcomes ◽  
Cross Validation ◽  
Activity Index ◽  
Joint Modeling ◽  
Joint Disease ◽  
Rheumatoid Arthritis Disease ◽  
Patient Reported ◽  
Over Time

Objective.To evaluate the performance of patient-reported outcomes (PRO) as primary indices for identification and prediction of a 28-joint Disease Activity Score (DAS28) > 3.2 among patients with rheumatoid arthritis (RA).Methods.Patients with RA completed monthly online PRO [Health Assessment Questionnaire (HAQ), Rheumatoid Arthritis Disease Activity Index (RADAI), visual analog scale (VAS) fatigue] and were clinically assessed every 3 months using the DAS28. Simple descriptive statistics, logistic regression, and the Bayesian joint modeling approach were used to analyze the data. The Bayesian joint model combines the scores and changes in the scores of 3 PRO to predict a DAS28 > 3.2 at the subsequent timepoint.Results.A group of 159 patients with RA participated. Stratified summaries of the PRO by DAS28 categories at baseline provided incremental values of the PRO for more active disease. However, on an individual level, the DAS28 and the PRO fluctuated over time. The prediction of subsequent DAS score by a single instrument at single timepoints resulted in moderate sensitivity and specificity. Using the intercept and slope of the combined PRO of the first 3 measurements to predict the DAS28 state at 3 months resulted in a sensitivity of 0.81 and a specificity of 0.92. After 10-fold cross validation, the model had a sensitivity of 0.61 and specificity of 0.75 to identify patients with a DAS28 > 3.2.Conclusion.PRO showed fluctuating levels of disease activity over time, while on a group level disease activity stayed the same. Using the changes in RADAI, HAQ, and VAS fatigue over time to predict future DAS28 > 3.2 resulted in moderate performance after the internal cross-validation of the model (sensitivity 0.61, specificity 0.75).

scholarly journals Comparative Analyses of Serological Biomarkers and Disease Characteristics between Elderly-onset and Younger-onset Rheumatoid Arthritis

2021 ◽  
Vol 16 (1) ◽  
pp. 237-245
Author(s):  
Rajalingham Sakthiswary ◽  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Functional Disability ◽  
Disease Duration ◽  
Severe Disease ◽  
Age At Onset ◽  
Health Assessment ◽  
Joint Damage ◽  
Study Data ◽  
Elderly Onset

The onset of rheumatoid arthritis (RA) may occur any time after the age of 16 years. The purpose of this study was to compare the clinical and serological differences between elderly onset RA (EORA); which is begins at the age of 60 and above, with younger onset RA (YORA). A total of 69 EORA and 82 YORA female patients were enrolled in this study. Data on medications, disease duration, age at onset, disease activity at onset and laboratory parameters were collected by reviewing the medical records. All patients had their blood samples taken for serum anticyclic citrulinated peptide (anti-CCP), IgA rheumatoid factor (RF), IgM RF and IgG RF. Besides, the subjects were assessed for their radiographic joint damage based on Modified Sharp Score (MSS) and functional disability based on the Health Assessment Questionnaire-disability Index (HAQ-DI) scores. Despite comparable disease duration and frequency of seropositivity, the YORA group had significantly higher disease activity at onset of the disease (p=0.009). In keeping with this finding, the YORA group had more severe joint damage based on radiographic assessment (MSS scores of 17.49+19.04 versus 10.04+12.79). The YORA group had significantly higher levels of IgA RF and anti-CCP with p-values of 0.035 and 0.002, respectively. Our findings suggest that YORA is associated with more severe disease, worse radiographic joint damage and higher levels of anti-CCP and IgA RF.

scholarly journals Cotreatment with methotrexate in routine care patients with rheumatoid arthritis receiving biological treatment yields better outcomes over time

RMD Open ◽  
2019 ◽  
Vol 5 (1) ◽  
pp. e000836 ◽  
Author(s):  
Niels W. Boone ◽  
Alexandre Sepriano ◽  
Paul-Hugo van der Kuy ◽  
Rob Janknegt ◽  
Ralph Peeters ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Combination Therapy ◽  
Disease Activity ◽  
Estimating Equation ◽  
Routine Care ◽  
Patient Reported Outcome ◽  
Joint Disease ◽  
Continuous Variables ◽  
Patient Reported ◽  
Over Time

ObjectivesWe aimed to evaluate the effects of methotrexate (MTX) comedication added to biological disease-modifying antirheumatic drugs (bDMARD) on disease activity measures in patients with rheumatoid arthritis (RA) in routine care.MethodsPatients with RA on treatment with either bDMARDs or conventional synthetic DMARDs were included in this prospective cohort study. The effect of (time-varying) combination therapy with bDMARD and MTX compared with bDMARD monotherapy was tested in longitudinal generalised estimating equation models using as outcomes: (1) the likelihood to be in remission according to the 28-joint Disease Activity Score (DAS28) erythrocyte sedimentation rate (ESR) (<2.6) and to the Routine Assessment of Patient Index Data 3 (RAPID3) (0–30; ≤3), a patient-reported outcome measure about RA symptoms; and (2) DAS28-ESR and RAPID3 as continuous variables. All models were adjusted for potential confounders: age, gender, drugs for comorbidities (yes/no), oral steroids (yes/no) and non-steroidal anti-inflammatory drug (yes/no).ResultsIn total, 330 patients were included (mean (SD) follow-up; 10.7 (9.7) months). Compared with bDMARD monotherapy, MTX combination therapy was significantly associated with a 55% higher likelihood to be in DAS28 remission, but not RAPID3 remission, over time. Combination therapy resulted in slightly, but statistically significant, lower levels of DAS28-ESR over time (β=−0.42 (95% CI −0.67 to − 0.17)), but not RAPID3 (β=−0.58 (95% CI −0.65 to 0.49)). The effect on DAS28-ESR was entirely explained by lower swollen joint counts and was persistent after correction for confounders.ConclusionThese results give support to the policy that MTX should be continued in routine care patients with RA on biological therapy since this leads to better objective but not subjective clinical outcomes

scholarly journals Lipids and Atherogenic Indices Fluctuation in Rheumatoid Arthritis Patients on Long-Term Tocilizumab Treatment

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Fabio Cacciapaglia ◽  
Maria Grazia Anelli ◽  
Angela Rinaldi ◽  
Marco Fornaro ◽  
Giuseppe Lopalco ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Joint Damage ◽  
Joint Disease ◽  
Atherogenic Index ◽  
Prolonged Treatment ◽  
Control Group ◽  
Long Term Treatment

Rheumatoid arthritis (RA) patients are at high risk of cardiovascular (CV) events, and the chronic inflammatory state may generate quantitative and qualitative changes in lipoprotein fractions. The anti-IL-6 receptor tocilizumab (TCZ), even if effective in inflammation and joint damage prevention, determined significant alterations to RA patients’ lipid levels in randomized controlled trials, but real-world data are lacking. We evaluated the changes in lipid fraction levels and disease activity in a longitudinal cohort of RA patients on long-term treatment with tocilizumab (TCZ) in a community setting. We retrospectively selected 40 naïve-biologic RA patients on treatment with intravenous TCZ compared to 20 RA patients on methotrexate treatment as the control group. Total cholesterol (Tot-Chol), low-density lipoproteins (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels were measured at the baseline and at 12, 24, and 52 weeks thereafter. At the same points, 28-joint disease activity score (DAS28), clinical disease activity index (CDAI), and EULAR clinical responses were also assessed. During the first 24 weeks, we observed in TCZ-treated patients a progressive statistically significant (p<0.001) increase in Tot-Chol, LDL, HDL, and TG, which returned close to the baseline at 52 weeks. But no changes in the lipid-related CV risk indices Tot-Chol/HDL and LDL/HDL ratios and the atherogenic index (log10 TG/HDL) were detectable. Notably, we observed a statistically significant negative correlation between changes in lipid fractions and DAS28 or CDAI. The prolonged treatment with TCZ was associated to a transient increase in cholesterol’s fractions during the first 6 months of treatment, with inverse correlation to disease activity, but with no impact on surrogate lipid indices of atherogenic risk. These findings may aid clinicians in interpreting the RA patient’s lipid profile in daily clinical practice.

Sleep Disturbances and Interleukin 6 Receptor Inhibition in Rheumatoid Arthritis

2011 ◽  
Vol 39 (1) ◽  
pp. 60-62 ◽  
Author(s):  
KALLIOPI FRAGIADAKI ◽  
MARIA G. TEKTONIDOU ◽  
MARIA KONSTA ◽  
GEORGE P. CHROUSOS ◽  
PETROS P. SFIKAKIS
Keyword(s):  
Rheumatoid Arthritis ◽  
Sleep Quality ◽  
Disease Activity ◽  
Interleukin 6 ◽  
Daytime Sleepiness ◽  
Sleep Disturbances ◽  
Functional Disability ◽  
Health Assessment ◽  
Joint Disease ◽  
Interleukin 6 Receptor

Objective.Interleukin 6 (IL-6)-mediated interactions have been associated with sleep disturbances in healthy subjects. In this pilot study we examined whether administration of the IL-6 receptor antagonist tocilizumab in patients with rheumatoid arthritis (RA) affects sleep disturbances.Methods.Fifteen patients (13 women) with sleep disturbances at baseline received 6 monthly infusions of tocilizumab 8 mg/kg for moderately or severely active RA. Sleep quality was assessed by Pittsburgh Sleep Quality Index (PSQI), daytime sleepiness by Epworth Sleepiness Scale, disease activity by the 28-joint Disease Activity Score-erythrocyte sedimentation rate, functional disability by Health Assessment Questionnaire Disability Index (HAQ-DI), and fatigue by the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue Scale; FFS) at baseline and first, second, third, and sixth month of treatment. Medications used before enrollment remained unchanged during followup.Results.Sleep quality improved and daytime sleepiness decreased significantly at first-month assessment (p < 0.00001 and p < 0.004, respectively, by repeated measurement analysis) compared to baseline, and these changes became more evident through 6 months. Disease activity decreased, fatigue decreased, and functional status improved significantly. Changes in PSQI score over time were not associated with the corresponding changes in DAS28-ESR (r = 0.37, p = 0.17), but correlated significantly with HAQ-DI changes (r = 0.60, p = 0.02) and marginally with changes in FFS scores (r = −0.46, p = 0.08).Conclusion.Improvement of sleep quality after tocilizumab treatment in patients with RA does not appear to directly result from decreased disease activity, further suggesting that aberrant IL-6 regulation is associated with sleep disturbances.

scholarly journals Circulating Semaphorin 4D as a Marker for Predicting Radiographic Progression in Patients with Rheumatoid Arthritis

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
You-Jung Ha ◽  
Dong Woo Han ◽  
Ji Hyoun Kim ◽  
Sang Wan Chung ◽  
Eun Ha Kang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Multivariate Logistic Regression Analysis ◽  
Serum Levels ◽  
Joint Disease ◽  
Semaphorin 4D ◽  
Reactive Protein ◽  
Baseline Levels

Semaphorin 3A (Sema3A) and semaphorin 4D (Sema4D) are molecules which regulate immune responses as well as bone remodeling process. The aim of this study was to evaluate the serum levels of Sema3A and Sema4D and to investigate their clinical significance in rheumatoid arthritis (RA). The serum levels of Sema3A and Sema4D were measured in 130 patients with RA and 65 sex- and age-matched healthy individuals. Circulating levels of biomarkers of RA-related inflammation and bone turnover such as tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, IL-22, IL-34, osteopontin, Dkk-1, and sclerostin were also measured. Disease activity was determined by the 28-joint disease activity score (DAS28), and radiographic joint damage was assessed by the modified Sharp van der Heijde score (SHS). The serum levels of Sema3A were significantly higher in patients with RA than those in healthy controls (p<0.001), whereas serum4D levels did not differ between the two groups. The levels of Sema4D showed a positive correlation with C-reactive protein (p=0.001) and IL-6 (p<0.001) levels, whereas the levels of Sema3A showed a negative correlation with Dkk-1 (p=0.007) and TNF-α (p=0.001). Even though Sema3A and Sema4D levels were comparable between RA patients with DAS28> 3.2 and with DAS28 ≤ 3.2, RA patients with radiographic progression (ΔSHS change/year ≥ 1) had significantly higher baseline levels of Sema4D than those without progression (p=0.029). Additionally, when RA patients were divided into 3 groups using tertiles of Sema4D levels, the percentage of progressors was significantly increased (p=0.045). In multivariate logistic regression analysis, serum Sema4D levels were an independent risk factor for radiographic progression. Our results suggest that the baseline levels of Sema4D might be a useful marker to identify RA patients with subsequent radiographic progression and that Sema4D may be an active mediator involved in RA-induced joint damage.

When to Adjust Therapy in Patients with Rheumatoid Arthritis After Initiation of Etanercept plus Methotrexate or Methotrexate Alone: Findings from a Randomized Study (COMET)

2014 ◽  
Vol 41 (10) ◽  
pp. 1922-1934 ◽  
Author(s):  
Maxime R. Dougados ◽  
Désirée M. van der Heijde ◽  
Yves Brault ◽  
Andrew S. Koenig ◽  
Isabelle S. Logeart
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Remission Rate ◽  
Randomized Study ◽  
Continuous Treatment ◽  
High Disease Activity ◽  
Joint Disease ◽  
Short Term ◽  
Short Term Treatment ◽  
Over Time

Objective.The objective of these posthoc analyses was to evaluate short-term clinical outcomes as predictors of poor response after 1 year of treatment with combination etanercept/methotrexate (ETN/MTX) therapy versus MTX monotherapy in patients with early rheumatoid arthritis (RA).Methods.Participants with moderate to severe RA [28-joint Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) ≥ 3.2] of 3–24 months’ duration received ETN 50 mg weekly plus MTX or MTX monotherapy for 52 weeks. Regression analyses were performed to evaluate the likelihood of remission (DAS28-ESR < 2.6) after 1 year despite poor clinical short-term treatment effects (e.g., absolute or changes from baseline in DAS28-ESR after 4, 8, 12, 20, and 24 weeks of therapy).Results.The magnitude of disease activity and its improvement and timing influenced remission probability in both treatment groups; remission rate was diminished with higher disease activity levels and lower response levels over time from weeks 4 to 24. The rate of DAS28-ESR remission at 1 year was generally greater with ETN/MTX than with MTX alone at most timepoints from weeks 4 to 24. Despite persistent high disease activity (DAS28-ESR > 5.1) after 4, 8, 12, and 24 weeks of therapy, 35%, 27%, 25%, and 22% of patients, respectively, in the ETN/MTX group achieved DAS28-ESR remission after 1 year of continuous treatment; the respective proportions were 33%, 27%, 8%, and 13% in the MTX group.Conclusion.High disease activity and less improvement with treatment over time in the initial 24 weeks of treatment, particularly after 12 weeks, were predictive of a lower remission rate after 1 year.

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