scholarly journals Fatigue is associated with disease activity in some, but not all, patients living with rheumatoid arthritis: disentangling “between-person” and “within-person” associations

2022 ◽  
Vol 6 (1) ◽  
Author(s):  
Grada A. Versteeg ◽  
Peter M. ten Klooster ◽  
Mart A. F. J. van de Laar
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Repeated Measures ◽  
Rating Scale ◽  
Pragmatic Trial ◽  
Tender Joint Count ◽  
Markers Of Inflammation ◽  
Patient Reported ◽  
Fatigue Severity ◽  
Over Time

Abstract Background Previous research has shown an unclear and inconsistent association between fatigue and disease activity in patients with rheumatoid arthritis (RA). The aim of this study was to explore differences in “between-person” and “within-person” associations between disease activity parameters and fatigue severity in patients with established RA. Methods Baseline and 3-monthly follow-up data up to one-year were used from 531 patients with established RA randomized to stopping (versus continuing) tumor necrosis factor inhibitor treatment enrolled in a large pragmatic trial. Between- and within-patient associations between different indicators of disease activity (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], swollen and tender joint count [ SJC and TJC], visual analog scale general health [VAS-GH]) and patient-reported fatigue severity (Bristol RA Fatigue Numerical Rating Scale) were disaggregated and estimated using person-mean centering in combination with repeated measures linear mixed modelling. Results Overall, different indices of disease activity were weakly to moderately associated with fatigue severity over time (β’s from 0.121 for SJC to 0.352 for VAS-GH, all p’s < 0.0001). Objective markers of inflammation (CRP, ESR and SJC) were associated weakly with fatigue within patients over time (β’s: 0.104–0.142, p’s < 0.0001), but not between patients. The subjective TJC and VAS-GH were significantly associated with fatigue both within and between patients, but with substantially stronger associations at the between-patient level (β’s: 0.217–0.515, p’s < 0.0001). Within-person associations varied widely for individual patients for all components of disease activity. Conclusion Associations between fatigue and disease activity vary largely for different patients and the pattern of between-person versus within-person associations appears different for objective versus subjective components of disease activity. The current findings explain the inconsistent results of previous research, illustrates the relevance of statistically distinguishing between different types of association in research on the relation between disease activity and fatigue and additionally suggest a need for a more personalized approach to fatigue in RA patients. Trial registration Netherlands trial register, Number NTR3112.

scholarly journals Trajectories of fatigue in actively treated patients with established rheumatoid arthritis starting biologic DMARD therapy

RMD Open ◽  
2020 ◽  
Vol 6 (3) ◽  
pp. e001372
Author(s):  
Sella Aarrestad Provan ◽  
Brigitte Michelsen ◽  
Joseph Sexton ◽  
Tillmann Uhlig ◽  
Hilde Berner Hammer
Keyword(s):  
Rheumatoid Arthritis ◽  
Rating Scale ◽  
Numeric Rating Scale ◽  
Tender Joint Count ◽  
Tender Joint ◽  
Logistic Regression Models ◽  
Patient Reported ◽  
Biologic Dmard ◽  
Clinically Significant

ObjectivesTo define fatigue trajectories in patients with rheumatoid arthritis (RA) who initiate biological DMARD (bDMARD) treatment, and explore baseline predictors for a trajectory of continued fatigue.MethodsOne-hundred and eighty-four patients with RA initiating bDMARDs were assessed at 0, 1, 2, 3, 6 and 12 months. Swollen and tender joint counts, patient reported outcomes (PROMs), blood samples and ultrasound examinations were collected at each time point. Fatigue was assessed by the fatigue Numeric Rating Scale (0–10) from the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire. Clinically significant fatigue was predefined as fatigue ≥4. Three trajectories of interest were defined according to level of RAID fatigue: no fatigue (≤3 at 5/6 visits), improved fatigue (≥4 at start, but ≤3 at follow-up) and continued fatigue (≥4 at 5/6 visits). Baseline variables were compared between groups by bivariate analyses, and logistic regression models were used to explore baseline predictors of continued vs improved fatigue.ResultsThe majority of patients starting bDMARD therapy followed one of three fatigue trajectories, (no fatigue; n=61, improved; n=33 and continued fatigue; n=53). Patients with continued fatigue were more likely to be anti–citrullinated protein antibody and/or rheumatoid factor positive and had higher baseline PROMs compared to the other groups, while there were no differences between the groups for variables of inflammation including. Patient global, tender joint count and anxiety were predictors for the continued fatigue trajectory.DiscussionA trajectory of continued fatigue was determined by PROMs and not by inflammatory RA disease activity.

scholarly journals FRI0020 CLINICAL TREATMENT RESPONSE STILL DOES NOT MATCH PATIENT REPORTED IMPROVEMENT, EVEN IN EARLY RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 582.1-582
Author(s):  
S. Pazmino ◽  
A. Lovik ◽  
A. Boonen ◽  
D. De Cock ◽  
V. Stouten ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Health Assessment ◽  
Sustained Remission ◽  
Research Support ◽  
Early Ra ◽  
Severity Scores ◽  
Patient Reported ◽  
Over Time

Background:Commonly used disease activity scores in rheumatoid arthritis (RA) include one patient reported outcome (PRO) -the patient’s global health assessment (PGA). Exploratory factor analysis (EFA) was performed on data from the 2 year Care in early Rheumatoid Arthritis (CareRA) trial to explain the evolution of disease burden extracting 3 factors.1Objectives:To assess the evolution and relative responsiveness over time of clinical, laboratory and patient assessments included in composite scores, together with other PROs like pain, fatigue and functionality in patients with early RA (≤1 year) treated to target (T2T) within the CareRA trial.Methods:DMARD naïve patients with early RA (n=379) were included, randomized to remission induction with COBRA-like treatment schemes (n=332) or MTX monotherapy (n=47) and T2T.Components of disease activity scores (swollen/tender joint count (S/TJC), C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR), and physician (PhGH) or patient (PGA) global health assessment), pain and fatigue (both on 0-100 scale) and HAQ were recorded at every visit.Missing data was handled with multiple imputation (n=15). Clustering was removed with multiple outputation (n=1000), then each of the 15 000 datasets was analyzed by EFA with principal component extraction and oblimin rotation. The analyses were combined after re-ordering the factors by maximizing factor congruence. The 3 extracted factors and their individual components (with their loadings) were: 1. Patient containing PGA (0.87), pain (0.86), fatigue (0.90) and HAQ (0.5) 2.Clinical with SJC (0.92), TJC (0.89) and PhGH (0.76) and 3.Laboratory with CRP(0.87) and ESR (0.78).1(Pazmino, ACR 2019 abstract, Table 3)Afterwards, variables were first normalized to a 0-1 scale, then multiplied -weighted- by the factor loadings previously obtained.1For each Patient, Clinical and Laboratory severity score, the weighted variables belonging to each score were summed together and then re-scaled to 0-1 (higher values suggest more burden).The percentage (%) improvement from baseline to week 104 and the area under the curve (AUC) across time points were calculated per factor.Differences in % improvement and AUC were compared between patients not achieving and achieving early and sustained (week 16 to 104) disease activity score remission (DAS28CRP <2.6) with ANOVA. Bonferroni correction was used for multiple testing.Results:Severity scores of Patient, Clinical and Laboratory factors improved rapidly over time (Figure 1). In patients achieving sustained remission (n=122), Patient, Clinical and Laboratory scores improved 56%, 90% and 27% respectively. In patients not achieving sustained remission (n=257) the improvement was 32%, 78% and 9% respectively (p<0.001 only for clinical improvement).Patients in CareRA who achieved sustained remission had an AUC of 15.1, 3.4 and 4.7 in Patient, Clinical and Laboratory scores respectively, compared to 32.3, 10.0, and 7.2 in participants not achieving sustained remission (p<0.001 for all comparisons).Conclusion:Patient, Clinical and Laboratory severity scores improved rapidly over time in patients achieving rapid and sustained disease control. However, overall, Patient burden seemed not to improve to the same extent as Clinical burden. Patient’s unmet needs in terms of pain, fatigue, functionality and overall well-being should thus be given more attention, even in patients in sustained remission.References:[1]Pazmino S,et al.Including Pain, Fatigue and Functionality Regularly in the Assessment of Patients with Early Rheumatoid Arthritis Separately Adds to the Evaluation of Disease Status [abstract]. ACR. 2019.Disclosure of Interests:Sofia Pazmino: None declared, Anikó Lovik: None declared, Annelies Boonen Grant/research support from: AbbVie, Consultant of: Galapagos, Lilly (all paid to the department), Diederik De Cock: None declared, Veerle Stouten: None declared, Johan Joly: None declared, Delphine Bertrand: None declared, Rene Westhovens Grant/research support from: Celltrion Inc, Galapagos, Gilead, Consultant of: Celltrion Inc, Galapagos, Gilead, Speakers bureau: Celltrion Inc, Galapagos, Gilead, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies

scholarly journals The Relation Between Disease Activity, Patient‐Reported Outcomes, and Grip Force Over Time in Early Rheumatoid Arthritis

2019 ◽  
Vol 1 (8) ◽  
pp. 507-515
Author(s):  
Maria Rydholm ◽  
Ingegerd Wikström ◽  
Sofia Hagel ◽  
Lennart T. H. Jacobsson ◽  
Carl Turesson
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Patient Reported Outcomes ◽  
Grip Force ◽  
Patient Reported ◽  
Over Time

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 Association between ultrasound images and patient-reported outcomes in the treatment of rheumatoid arthritis: a retrospective study

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Masao Nawata ◽  
Kazuki Someya ◽  
Masashi Funada ◽  
Yuya Fujita ◽  
Atsushi Nagayasu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Multivariate Analysis ◽  
Disease Activity ◽  
Patient Reported Outcomes ◽  
Tender Joint Count ◽  
Ultrasound Images ◽  
Treatment Goals ◽  
Vas Score ◽  
Patient Reported ◽  
The Relationship

Abstract Background Improvements in the treatment of rheumatoid arthritis (RA) have made it possible to achieve treatment goals. It has been reported that both residual synovitis caused by RA and the patients’ subjective symptoms remain even after achieving the treatment goals; however, there are limited reports showing a relationship between them. Furthermore, no studies have evaluated the relationship between patient-reported outcomes (PROs) and subclinical synovitis measured by musculoskeletal ultrasonography (MSUS) in the treatment of RA. This study aimed to investigate residual symptoms and residual synovitis due to remission (REM) or low disease activity (LDA). Methods We performed MSUS on 300 patients with RA who attended our hospital for routine care, and we analysed them cross-sectionally by disease activity. Grayscale (GS) and power Doppler (PD) synovitis was evaluated in 22 bilateral hand joints using MSUS. We first performed univariate and multivariate analysis by dividing the data by disease activity. Next, we analysed each PRO in the obtained MSUS results. Results A multivariate analysis of high disease activity (HDA)/moderate disease activity (MDA) vs. LDA/ REM group identified tender joint count (TJC), pain visual analog scale (VAS) score, and presence or absence of GS score ≥ 2. The one-way analysis of the relationship between the presence or absence of GS score ≥ 2 and each PRO showed a significant difference. In contrast, a multivariate analysis of LDA vs. REM group identified TJC and fatigue VAS score. In REM, PROs alone were relevant, and there was no correlation with MSUS. Conclusion We found that the residual inflammation in the ultrasound images was associated with PROs in the LDA group, but not in the REM group. Trial registration Retrospectively registered.

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 POS0616 LONG-TERM EFFECTIVENESS AFTER MULTIPLE CYCLES WITH RITUXIMAB FOLLOWING AN ON-FLARE RETREATMENT STRATEGY IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 545-546
Author(s):  
D. Bertrand ◽  
N. Pype ◽  
T. Conings ◽  
D. De Cock ◽  
S. Pazmino ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Global Health ◽  
Adverse Events ◽  
Disease Activity ◽  
University Hospital ◽  
C Cycle ◽  
Patient Reported ◽  
Efficacious Drug ◽  
Over Time

Background:Rituximab is known as an efficacious drug for the treatment of Rheumatoid Arthritis (RA). The recommended administration schedule consist of 2 infusions of 1000 mg with a 2-week interval. In Belgium an on-flare retreatment strategy is followed, making evaluation of effectiveness over time challenging. Moreover the patient’s view on this strategy is unclear.Objectives:To explore long-term effectiveness and safety of rituximab in daily clinical practice in patients with RA.Methods:Data of patients diagnosed with RA and treated with rituximab in a tertiary university hospital were retrospectively collected. For every cycle, clinical data were recorded at the time of the first and second infusion, the 16-week visit and the visit on which the treating rheumatologist decided to prescribe a new cycle. Data on demographics, previous RA treatment, disease activity, patient-reported outcomes, adverse events related to rituximab, dose and number of cycles were collected from 01/01/2006 until 01/12/2019 or until discontinuation of rituximab. The visit on which rituximab was prescribed for the first time was considered as the baseline visit. The data were analysed descriptively.Results:Data of 66 patients with RA were collected. The median (IQR) age was 57.0 (47.0-65.0) years at baseline and 56% (37/66) were female. Most patients were seropositive (RF 91% and ACPA 92%), and had erosive (71%) or nodular disease (53%). The median (IQR) disease duration was 12.5 (4.0-18.3) years. In total, 94% of the patients had failed at least one other biological Disease-modifying Antirheumatic Drug (bDMARD) before starting rituximab. Overall, patients received a median (IQR) of 3 (2-7) cycles of rituximab. Seven of the 66 patients (11%) discontinued rituximab and changed to another bDMARD after a median (IQR) of 1 (1-6) cycles and 11% were treated with a lower dose than 2x1000mg. The median (IQR) interval between the first 2 cycles was 7.0 (6.0-10.0) months, after which this increased to up to one year (interval between cycle 2-3: 10.0 (7.0-13.0) months, cycle 3-4: 12.0 (7.3-15.5) months). The overall median (IQR) follow-up time was 45.5 (14.8-82.3) months. The efficacy of rituximab remained after repeated cycles: after every treatment with rituximab, a reduction in disease activity based on the disease activity score in 28 joints (DAS28) could be noticed (figure 1A). The evolution in patients’ (PaGH) and physicians’ global health (PhGH) assessment followed the same pattern as the DAS28-score (Figure 1B). High PaGH-scores could be noticed at every start of a new rituximab cycle. The proportion of patients with a PaGH-score above 20 ranged from 84% - 100%, 74% - 100% and 66% - 86% at the first infusion, second infusion and week 16 visits, respectively. Rituximab was considered to be well-tolerated. In total, 23 adverse events in 12 patients were recorded and none of them were serious.Conclusion:Rituximab can be considered a highly efficacious drug for RA treatment in daily practice. There were no major side effects and there was an increasing treatment interval over time. However, a healthy survivor effect should be kept in mind when interpreting the results. It should be noted that with the on-flare retreatment strategy, every new rituximab cycle was preceded by a rise in PaGH-scores, which reflects a state of impaired wellbeing reported by patients. This should be further studied with qualitative methods and in a randomized trial setting comparing on-flare with fixed-interval retreatment to evaluate optimal effectiveness.Figure 1.Evolution in median - interquartile range disease activity (DAS28CRP) (A) and patients’ (PaGH) and physicians’ global health (PhGH) (B) over the different rituximab cycles. The disease activity, PaGH and PhGH were measured at baseline, the time of the first and second infusion, W16 and the visit on which a new rituximab cycle was prescribed. The dotted lines represent a DAS28CRP-score of 2.6 (remission cut-off) and 3.2 (low disease activity cut-off). C: cycle; W: week; VAS: visual analogue scale.Disclosure of Interests:None declared

scholarly journals Patient-reported fatigue in patients with rheumatoid arthritis who commence biologic therapy: a longitudinal study

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6771 ◽  
Author(s):  
Hege Selheim Rinke ◽  
Clara Beate Gram Gjesdal ◽  
Heidi Markussen ◽  
Jörg Assmus ◽  
Gerd Karin Natvig
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Repeated Measures ◽  
Biologic Therapy ◽  
Well Being ◽  
Biologic Treatment ◽  
Emotional Factors ◽  
Female Sex ◽  
Paired Samples ◽  
Patient Reported

Aims and objectives To examine changes in patient-reported fatigue, over a twelve month period, in rheumatoid arthritis patients who commence biologic treatment, and to identify possible predictors for such changes. Background Fatigue is a burdensome symptom for patients with rheumatoid arthritis. Despite biologics being effective in reducing disease activity, patients still report fatigue. Design A longitudinal observational study. Methods A total of 48 patients were enrolled in the study. Fatigue was measured by the Fatigue Severity Scale. Independent samples T-tests were used to test gender differences, and paired samples T-tests were used to measure differences between repeated measures. Bivariate and multiple regression analyses were used to examine potential predictors for changes in fatigue, such as age, sex, Disease Activity Score 28, pain and physical and emotional well-being. Results Forty-seven patients completed the study. From baseline to 12-month follow-up, fatigue decreased significantly in both women and men. Analyses of predictors were performed step-wise, and the final model included sex and physical well-being. The results from this final step showed that female sex was the only significant predictor for changes in fatigue. Conclusion Patients commencing biologic therapy reported a significant reduction in fatigue. Female sex was a significant predictor of changes in fatigue. Relevance to clinical practice Despite improvements in pharmacological treatment, patients with rheumatoid arthritis still report fatigue. This is a multifaceted health problem encompassing personal and emotional factors in addition to the clinical factors directly connected to the disease.

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